Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Nikita Wright
 + 2308 word(s) 2308 2021-12-22 09:48:22 |
2 format correct
Conner Chen
 Meta information modification 2308 2022-01-07 02:03:11 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Wright, N. Kinesin Family Member C1 (KIFC1/HSET) and Breast Cancer. Encyclopedia. Available online: https://encyclopedia.pub/entry/17840 (accessed on 29 July 2024).
Wright N. Kinesin Family Member C1 (KIFC1/HSET) and Breast Cancer. Encyclopedia. Available at: https://encyclopedia.pub/entry/17840. Accessed July 29, 2024.
Wright, Nikita. "Kinesin Family Member C1 (KIFC1/HSET) and Breast Cancer" Encyclopedia, https://encyclopedia.pub/entry/17840 (accessed July 29, 2024).
Wright, N. (2022, January 06). Kinesin Family Member C1 (KIFC1/HSET) and Breast Cancer. In Encyclopedia. https://encyclopedia.pub/entry/17840
Wright, Nikita. "Kinesin Family Member C1 (KIFC1/HSET) and Breast Cancer." Encyclopedia. Web. 06 January, 2022.
Kinesin Family Member C1 (KIFC1/HSET) and Breast Cancer
Edit
This entry is adapted from the peer-reviewed paper 10.3390/jpm11121361

Breast carcinogenesis involves a series of key molecular deregulatory events that prompt normal cells to bypass tumor-suppressive senescence barriers. Kinesin family member C1 (KIFC1/HSET), a microtubule binding protein of the kinesin-14 family, prevents the death of cells with centrosome amplification (CA), which is a hallmark of cancer. Kinesin family member C1 (KIFC1/HSET), which confers survival of cancer cells burdened with extra centrosomes, has been observed in premalignant and pre-invasive lesions, and its expression has been shown to correlate with increasing neoplastic progression. Additionally, KIFC1 has been associated with aggressive breast tumor molecular subtypes, such as basal-like and triple-negative breast cancers.

breast cancer kinesin family member C1 (KIFC1/HSET) centrosome amplification neoplastic progression tumorigenesis human mammary epithelial cells (HMECs)

1. Introduction

Breast cancer is the leading form of cancer diagnosed among women in the United States [1]. Approximately 1 in 8 American women are expected to develop breast cancer in their lifetime [1][2]. Among women under the age of 40, Black/African-American women have higher incidence rates of breast cancer and are more likely to die from breast cancer overall than non-Hispanic White women [1]. Furthermore, Black/African-American women disproportionately present in the clinic with the most aggressive breast tumor subtypes, such as basal-like and triple-negative breast cancers (TNBC) [1][3][4].
The development of breast cancer has been shown to require a multistep process that involves a series of key transformative events [5][6][7]. These stages of progression have been clinically classified as ductal hyperplasia (DH) and atypical hyperplasia (AH), which reflect early histologically identifiable neoplastic changes; these stages are believed to progress to carcinoma in situ (CIS) and invasive carcinoma (IC), which reflect a transition to malignancy and tumor progression, respectively [8][9]. The critical molecular events underlying the development of each stage, also known as aging, have been shown to primarily involve the bypassing of three distinct tumor-suppressive barriers in human mammary epithelial cells (HMECs), including stress-associated stasis, replicative senescence, and oncogene-induced senescence [10][11][12]. Bypassing these crucial barriers, which involves loss of genomic integrity, cell cycle dysregulation, and telomerase reactivation, allows normal healthy cells to become immortalized or malignant [6][7]. However, no routinely assessable robust radiologic, pathologic, or molecular biomarkers currently exist in the clinic to predict the likelihood of a patient’s lesion progressing to a malignant state and becoming invasive or bypassing critical tumor-suppressive barriers. Additionally, no such biomarkers exist that can predict the intrinsic subtype of a transformed lesion.
Kinesin family member C1 (KIFC1/HSET), a microtubule binding protein of the kinesin-14 family, prevents the death of cells with centrosome amplification (CA), which is a hallmark of cancer [13][14]. CA (when a cell harbors three or more centrosomes or abnormally large centrosomes) has been observed in premalignant and pre-invasive lesions and postulated to drive pre-neoplastic changes in early stage lesions and tumor progression [14][15][16][17]. In HMECs and stem cells, CA was found to increase with age [18][19]. Specifically, CA has been found to increase from atypical ductal hyperplasia (ADH) to ductal carcinoma in situ (DCIS), to increase with higher DCIS grade, and to be more prevalent in TNBC versus non-TNBC tumors [20][21]. CA has also been shown to be associated with chromosomal instability (CIN) and aneuploidy in early stage breast lesions as well as being linked to cell cycle deregulation, telomere dysfunction, and cellular senescence [15][16][22][23][24][25]. Furthermore, induction of CA in non-transformed cell lines has been shown to be sufficient to induce tumorigenesis and to mimic oncogene-induced cellular invasion [26][27][28][29]. KIFC1 is upregulated upon induction of CA in cancer cells as a compensatory mechanism that assists cancer cells with extra centrosomes to avoid undergoing cell death [30]. Supernumerary centrosomes promote multipolar mitotic cellular divisions, which could result in levels of aneuploidy that could prevent the progeny cells from surviving. KIFC1 can circumvent this cell death by clustering extra centrosomes for proper cell division. Thus, KIFC1 upregulation has been linked to the survival and expansion of genomically unstable cells. Persistence of cells with loss of genomic integrity may promote the ability of pre-neoplastic cells to initiate early neoplastic changes, transformation, and progression.
KIFC1 is overexpressed and confers a poorer prognosis across various cancer types such as hepatocellular carcinoma, non-small cell lung cancer, ovarian cancer, prostate cancer, and breast cancer [31][32][33][34]. In breast cancer, high nuclear KIFC1 levels at the time of diagnosis have been associated with shorter overall and progression-free survival [35]. Breast tumors display approximately five-fold higher KIFC1 expression compared to corresponding normal tissue, and KIFC1 is specifically upregulated in estrogen receptor-negative breast tumors and TNBC [35][36]. KIFC1 expression was also found to be higher in breast cancer cell lines compared to premalignant cells, such as the MCF10A series and HMECs [35][36]. KIFC1 expression was found to be low in normal HMECs and in normal breast epithelia tissue [35][36]. However, a progressive increase in nuclear KIFC1 expression was observed from DH to ADH to DCIS and to IC and also correlated with increasing tumor grade [35].
Since nuclear accumulation of KIFC1 (a) is present in early stage lesions, (b) increases with progressive stages of neoplastic transformation, (c) is linked to key processes in malignant transformation, and (d) facilitates the evasion of cell death, we postulate that nuclear KIFC1 may be a potential biomarker of oncogenic transformation and predict the likelihood of a premalignant or pre-invasive lesion progressing in the clinic. KIFC1 can also be more easily assessed than CA among high-risk patients in the clinic through clinically facile methods such as immunohistochemistry (IHC) since CA is an organellular abnormality and not a protein like KIFC1. Furthermore, KIFC1 inhibition, which selectively targets cells harboring CA, has been shown to be an effective minimally cytotoxic anti-cancer strategy in preclinical studies [37]. This finding suggests that KIFC1 inhibitors may be a potential treatment option for high-risk patients with premalignant or pre-invasive lesions to prevent progression.

2. Bypassing the Stress-Associated Stasis Barrier: KIFC1 and Cell Cycle Deregulation

Since the centrosome organizes microtubules for proper cell division, centrosome number fidelity is critical for equal partitioning of chromosomes into each daughter cell [38][39]. Cells burdened with extra centrosomes will often form three or more spindle poles during mitoses in lieu of a bipolar spindle [15][16]. This organellar abnormality and microtubule disorganization can result in cytoarchitectural alterations in tissue, leading to loss of cellular differentiation (anaplasia) [40]. Furthermore, this erroneous multipolar mitosis can lead to unequal segregation of chromosomes into each daughter cell and subsequently intolerable levels of aneuploidy. To avoid this error, cells will undergo mitotic arrest or mitotic catastrophe and activate apoptotic or necrotic cell death machinery [41][42]. However, KIFC1, which is a minus-end-directed microtubule binding protein that is activated by genomic instability signals, associates with the plus ends of microtubules and translocates to the nucleus, where it crosslinks and slides microtubules in an antiparallel fashion [43][44]. This antiparallel sliding allows extra centrosomes to aggregate at opposite poles of the cells to still form a “pseudo-bipolar spindle”, which results in the occurrence of lagging chromosomes [13][45][46]. This “pseudo-bipolar” spindle can thus allow premalignant or pre-invasive cancer cells to avert mitotic arrest and cell death so they can continue replicating as genomically unstable cells. This phenomenon can increase the genetic diversity among the cellular population [47]. This phenotypic heterogeneity in lesions can promote the selection of viable cellular subclones with advantageous traits and precipitate the expansion of more aggressive cellular phenotypes [47][48]. Hence, KIFC1-mediated centrosome clustering may be a key factor driving the survival of cells in benign lesions that are more likely to transform to a malignant state and progress.
CA has been shown to increase in normal HMECs with continued population doublings [49][50]. As previously discussed, normal HMECs that have bypassed the stasis barrier exhibit significant deregulation of the universal regulators of cell cycle control, Rb or p53. Centrosomes normally duplicate in the S phase of the cell cycle [51]. Activated Rb represses the E2F1-mediated gene transcription required for G1 to S phase transition, and p53 can halt cell division in the G1 phase by inhibiting CDK activity [52]. Centrosome duplication is tightly coordinated with genome duplication and cell division [16]. Thus, loss of Rb and p53 function along with downstream p16 and p21 loss has been shown to generate supernumerary centrosomes [49][53][54][55]. This induction of CA can lead to the selection of cells with upregulation of KIFC1 to prevent spindle multipolarity and death of progeny cells. KIFC1 expression was found to be higher in p53 mutant or null tumors compared to p53 wild-type tumors [56]. Inhibition of KIFC1 gene expression was shown to upregulate p21 and downregulate CDK2 to arrest cells in G2–M phases [32]. Furthermore, KIFC1 depletion in primary human fibroblast cells displayed features of senescence, such as β-galactosidase expression [57]. These findings suggest that KIFC1 may be upregulated as a result of Rb or p53 deregulation to allow genomically unstable cells to continue replicating and avoid cellular senescence. Thus, KIFC1 may play a key role in conferring normal HMECs, deregulated in Rb or p53, the ability to continue replicating and therefore successfully bypass the stasis barrier. An Rb loss-of-function signature was established in The Cancer Genome Atlas by identifying genes that correlate with E2F1 and E2F2 expression in breast cancer, and KIFC1 emerged as one of the top genes included in the signature [58].
KIFC1 may help pre-neoplastic cells bypass the stasis barrier through alternative mechanisms. KIFC1 may assist cells with CA that activate p53, as a result of causing mitotic defects, to avert apoptosis, allowing these cells to persist [47]. Additionally, KIFC1 has been shown to protect the apoptosis resistance protein survivin from degradation by E3 ligase APC/C [35]. KIFC1 overexpression in cancer cells was found to accelerate cell cycle kinetics, particularly from G2 to M phase. Specifically, KIFC1 overexpression upregulated survival signals such as phosphorylated Bcl2, Aurora B kinase, cyclin B1, D1, and A [35]. Cyclin D1 overexpression in particular has been shown to facilitate bypassing of the stasis barrier in normal HMECs [35][59].

3. Bypassing the Replicative Cellular Senescence Barrier: KIFC1 and Loss of Telomere Function and Genomic Stability

As previously discussed, the ability of normal or post-stasis HMECs to correct telomere dysfunction or continue replicating with critically shortened telomeres can allow this subset of cells to bypass the second and one of the most important senescence barriers to immortalization. Telomere dysfunction as a result of telomere attrition (critical shortening of chromosomal telomeres), also known as replicative senescence, has been shown to elicit genomic instability/CIN and activation of DNA damage response repair pathways. Specifically, telomere dysfunction can induce breakage–fusion–bridge cycles that can cause structural and numerical chromosomal aberrations resulting in CIN and aneuploidy [23][60].
However, evidence exists suggesting that centrosomal aberrations precede the emergence of TP53 mutations and end-to-end fusions during early carcinogenesis [16][61]. Telomere dysfunction has been suggested to induce supernumerary centrosomes and shown to directly correlate with increased levels of CA in HMECs, cancer cell lines, and tumor tissue. Specifically, genotoxic stress-mediated telomere dysfunction via perturbation of p16 activity in post-stasis HMECs induced the presence of centriole overduplication [50]. This stimulation of telomere dysfunction via genotoxic stress promoted localization of telomerase transcriptional elements-interacting factor (TEIF), a transactivator of human telomerase reverse transcriptase subunit, to the centrosome and induced CA [24]. TEIF was found to positively correlate with CA in colorectal tumors [62]. Telomere dysfunction induced in Drosophila oogenesis caused deregulation of centrosome biogenesis, leading to embryonic lethality [22]. Since CA also elicits CIN and genomic instability, telomere dysfunction may cause CIN and aneuploidy to arise in pre-neoplastic HMECs or early stage lesions.
KIFC1 is possibly upregulated upon induction of CA as a result of telomere dysfunction. This upregulation can confer a survival advantage among cells with dysfunctional telomeres. Thus, KIFC1 may promote the survival of cells with loss of telomere function. Therefore, KIFC1 may act as a key player in facilitating pre-neoplastic cells that have acquired telomere abnormalities to bypass the replicative cellular senescence barrier. Inhibiting KIFC1, and subsequently declustering extra centrosomes, could potentially induce apoptosis of telomere-dysfunctional cells. KIFC1 phosphorylation induced upon DNA damaging agent treatment conferred cancer cell resistance to this therapy, and inhibition of this KIFC1 phosphorylation repressed centrosome clustering and tumor recurrence [63]. An alternative theory on KIFC1′s potential role in bypassing this senescence barrier is that through its involvement in promoting phenotypic diversity, it may be fostering the survival of subcellular clones that selectively reactivate telomerase.

4. Bypassing the Oncogene-Induced Senescence Barrier: KIFC1 and Ras Signaling

The mechanisms underlying oncogene-induced senescence remain poorly elucidated. However, HMECs that have attained immortality via reactivation of telomerase are not vulnerable to this senescence barrier but exhibit the acquisition of malignant properties after overexpression of Raf-1, Ras, or ErbB2 [64]. Induction of K-Ras, alone or co-expressed with c-Myc (transcription factor downstream of Ras signaling), was shown to induce CA in premalignant human mammary glands and HMECs via dysregulation of key regulators of the centrosome duplication cycle, Cyclin D1/CDK4 and Nek2 [65]. Transduction of post-stasis HMECs with c-myc was shown to promote bypassing of the replicative senescence barrier [59]. Thus, KIFC1 may be upregulated upon Ras-induced CA and thereby confer survival of these cells. Knockdown of KIFC1 was found to inhibit the MAPK signaling cascade and downstream signaling, suggesting that KIFC1 inhibition may abrogate Ras-induced CA. These findings suggest that HMECs upregulated in oncogenic Ras signaling may be bypassing the oncogenic-induced senescence barrier by upregulating KIFC1 as a mechanism to cope with Ras-stimulated CA.
The epithelial–mesenchymal transition (EMT) process confers mesenchymal characteristics that impart invasive capabilities [66]. The EMT process is marked by loss of the epithelial cell junction protein E-cadherin and upregulation of the transcriptional factors N-cadherin, Snail, and ZEB1. Downregulation of E-cadherin is necessary for KIFC1 to efficiently cluster extra centrosomes by increasing cortical contractility [67]. Thus, low clustering capacity was found to correlate with high levels of E-cadherin. Knockdown of KIFC1 increased expression of E-cadherin and decreased expression of N-cadherin, Snail, and ZEB1 in cancer cells [68]. Thus, the existence of CA and concomitant upregulation of KIFC1 in pre-invasive lesions may also be accompanied by loss of E-cadherin at cell–cell junctions, thereby additionally imparting the ability to invade surrounding tissue to these lesions. Hence, KIFC1-mediated centrosome clustering may impart invasive capabilities to pre-invasive cells via downregulation of E-cadherin.

References

  1. DeSantis, C.; Ma, J.; Bryan, L.; Jemal, A. Breast cancer statistics, 2013. CA Cancer J. Clin. 2014, 64, 52–62.
  2. Ganz, P.A.; Goodwin, P.J. Breast Cancer Survivorship: Where Are We Today? Adv. Exp. Med. Biol. 2015, 862, 1–8.
  3. Troester, M.A.; Sun, X.; Allott, E.H.; Geradts, J.; Cohen, S.M.; Tse, C.K.; Kirk, E.L.; Thorne, L.B.; Mathews, M.; Li, Y.; et al. Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study. J. Natl. Cancer Inst. 2018, 110, 176–182.
  4. Huo, D.; Hu, H.; Rhie, S.K.; Gamazon, E.R.; Cherniack, A.D.; Liu, J.; Yoshimatsu, T.F.; Pitt, J.J.; Hoadley, K.A.; Troester, M.; et al. Comparison of Breast Cancer Molecular Features and Survival by African and European Ancestry in The Cancer Genome Atlas. JAMA Oncol. 2017, 3, 1654–1662.
  5. Russo, J.; Calaf, G.; Sohi, N.; Tahin, Q.; Zhang, P.L.; Alvarado, M.E.; Estrada, S.; Russo, I.H. Critical Steps in Breast Carcinogenesis. Ann. N. Y. Acad. Sci. 1993, 698, 1–20.
  6. Russo, J.; Russo, I.H. The Pathway of Neoplastic Transformation of Human Breast Epithelial Cells. Radiat. Res. 2001, 155, 151–154.
  7. Russo, J.; Yang, X.; Hu, Y.F.; Bove, B.A.; Huang, Y.; Silva, I.D.; Tahin, Q.; Wu, Y.; Higgy, N.; Zekri, A.; et al. Biological and Molecular Basis of Human Breast Cancer. Front. Biosci. 1998, 3, D944–D960.
  8. Russo, J.; Calaf, G.; Russo, I.H. A Critical Approach to the Malignant Transformation of Human Breast Epithelial Cells with Chemical Carcinogens. Crit. Rev. Oncog. 1993, 4, 403–417.
  9. Page, D.L.; Dupont, W.D. Anatomic Markers of Human Premalignancy and Risk of Breast Cancer. Cancer 1990, 66, 1326–1335.
  10. Garbe, J.C.; Bhattacharya, S.; Merchant, B.; Bassett, E.; Swisshelm, K.; Feiler, H.S.; Wyrobek, A.J.; Stampfer, M.R. Molecular Distinctions between Stasis and Telomere Attrition Senescence Barriers Shown by Long-Term Culture of Normal Human Mammary Epithelial Cells. Cancer Res. 2009, 69, 7557–7568.
  11. Garbe, J.C.; Holst, C.R.; Bassett, E.; Tlsty, T.; Stampfer, M.R. Inactivation of p53 Function in Cultured Human Mammary Epithelial Cells Turns the Telomere-Length Dependent Senescence Barrier from Agonescence into Crisis. Cell Cycle 2007, 6, 1927–1936.
  12. Garbe, J.C.; Vrba, L.; Sputova, K.; Fuchs, L.; Novak, P.; Brothman, A.R.; Jackson, M.; Chin, K.; LaBarge, M.A.; Watts, G.; et al. Immortalization of Normal Human Mammary Epithelial Cells in Two Steps by Direct Targeting of Senescence Barriers Does not Require Gross Genomic Alterations. Cell Cycle 2014, 13, 3423–3435.
  13. Cai, S.; Weaver, L.N.; Ems-McClung, S.C.; Walczak, C.E. Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Length by Cross-Linking and Sliding Microtubules. Mol. Biol. Cell 2009, 20, 1348–1359.
  14. Chan, J.Y. A Clinical Overview of Centrosome Amplification in Human Cancers. Int. J. Biol. Sci. 2011, 7, 1122–1144.
  15. D’Assoro, A.B.; Lingle, W.L.; Salisbury, J.L. Centrosome Amplification and the Development of Cancer. Oncogene 2002, 21, 6146–6153.
  16. Lingle, W.L.; Barrett, S.L.; Negron, V.C.; D’Assoro, A.B.; Boeneman, K.; Liu, W.; Whitehead, C.M.; Reynolds, C.; Salisbury, J.L. Centrosome Amplification Drives Chromosomal Instability in Breast Tumor Development. Proc. Natl. Acad. Sci. USA 2002, 99, 1978–1983.
  17. Lopes, C.A.M.; Mesquita, M.; Cunha, A.I.; Cardoso, J.; Carapeta, S.; Laranjeira, C.; Pinto, A.E.; Pereira-Leal, J.B.; Dias-Pereira, A.; Bettencourt-Dias, M.; et al. Centrosome Amplification Arises before Neoplasia and Increases Upon p53 Loss in Tumorigenesis. J. Cell Biol. 2018, 217, 2353–2363.
  18. Sridharan, D.M.; Enerio, S.; LaBarge, M.A.; Stampfer, M.M.; Pluth, J.M. Lesion Complexity Drives Age Related Cancer Susceptibility in Human Mammary Epithelial Cells. Aging (Albany NY) 2017, 9, 665–686.
  19. Park, J.S.; Pyo, J.H.; Na, H.J.; Jeon, H.J.; Kim, Y.S.; Arking, R.; Yoo, M.A. Increased Centrosome Amplification in Aged Stem Cells of the Drosophila Midgut. Biochem. Biophys Res. Commun. 2014, 450, 961–965.
  20. Niu, Y.; Liu, T.; Tse, G.M.; Sun, B.; Niu, R.; Li, H.M.; Wang, H.; Yang, Y.; Ye, X.; Wang, Y.; et al. Increased Expression of Centrosomal Alpha, Gamma-Tubulin in Atypical Ductal Hyperplasia and Carcinoma of the Breast. Cancer Sci. 2009, 100, 580–587.
  21. Pannu, V.; Mittal, K.; Cantuaria, G.; Reid, M.D.; Li, X.; Donthamsetty, S.; McBride, M.; Klimov, S.; Osan, R.; Gupta, M.V.; et al. Rampant Centrosome Amplification Underlies more Aggressive Disease Course of Triple Negative Breast Cancers. Oncotarget 2015, 6, 10487–10497.
  22. Morgunova, V.; Kordyukova, M.; Mikhaleva, E.A.; Butenko, I.; Pobeguts, O.V.; Kalmykova, A. Loss of Telomere Silencing Is Accompanied by Dysfunction of Polo Kinase and Centrosomes during Drosophila Oogenesis and Early Development. PLoS ONE 2021, 16, e0258156.
  23. Pampalona, J.; Frias, C.; Genesca, A.; Tusell, L. Progressive Telomere Dysfunction Causes Cytokinesis Failure and Leads to the Accumulation of Polyploid Cells. PLoS Genet. 2012, 8, e1002679.
  24. Gong, Y.; Sun, Y.; McNutt, M.A.; Sun, Q.; Hou, L.; Liu, H.; Shen, Q.; Ling, Y.; Chi, Y.; Zhang, B. Localization of TEIF in the Centrosome and its Functional Association with Centrosome Amplification in DNA Damage, Telomere Dysfunction and Human Cancers. Oncogene 2009, 28, 1549–1560.
  25. Wu, Q.; Li, B.; Liu, L.; Sun, S.; Sun, S. Centrosome Dysfunction: A Link between Senescence and Tumor Immunity. Signal Transduct. Target. Ther. 2020, 5, 107.
  26. Basto, R.; Brunk, K.; Vinadogrova, T.; Peel, N.; Franz, A.; Khodjakov, A.; Raff, J.W. Centrosome Amplification Can Initiate Tumorigenesis in Flies. Cell 2008, 133, 1032–1042.
  27. Godinho, S.A.; Picone, R.; Burute, M.; Dagher, R.; Su, Y.; Leung, C.T.; Polyak, K.; Brugge, J.S.; Thery, M.; Pellman, D. Oncogene-like Induction of Cellular Invasion from Centrosome Amplification. Nature 2014, 510, 167–171.
  28. Levine, M.S.; Bakker, B.; Boeckx, B.; Moyett, J.; Lu, J.; Vitre, B.; Spierings, D.C.; Lansdorp, P.M.; Cleveland, D.W.; Lambrechts, D.; et al. Centrosome Amplification Is Sufficient to Promote Spontaneous Tumorigenesis in Mammals. Dev. Cell 2017, 40, 313–322.e5.
  29. Denu, R.A.; Zasadil, L.M.; Kanugh, C.; Laffin, J.; Weaver, B.A.; Burkard, M.E. Centrosome Amplification Induces High Grade Features and Is Prognostic of Worse Outcomes in Breast Cancer. BMC Cancer 2016, 16, 47.
  30. Quintyne, N.J.; Reing, J.E.; Hoffelder, D.R.; Gollin, S.M.; Saunders, W.S. Spindle Multipolarity Is Prevented by Centrosomal Clustering. Science 2005, 307, 127–129.
  31. Fu, X.; Zhu, Y.; Zheng, B.; Zou, Y.; Wang, C.; Wu, P.; Wang, J.; Chen, H.; Du, P.; Liang, B.; et al. KIFC1, a Novel Potential Prognostic Factor and Therapeutic Target in Hepatocellular Carcinoma. Int. J. Oncol. 2018, 52, 1912–1922.
  32. Liu, Y.; Zhan, P.; Zhou, Z.; Xing, Z.; Zhu, S.; Ma, C.; Li, Q.; Zhu, Q.; Miao, Y.; Zhang, J.; et al. The Overexpression of KIFC1 Was Associated with the Proliferation and Prognosis of Non-Small Cell Lung Cancer. J. Thorac. Dis. 2016, 8, 2911–2923.
  33. Sun, Y.; Zhang, Y.; Lang, Z.; Huang, J.; Zou, Z. Prognostic and Clinicopathological Significance of Kinesin Family Member C1 in Various Cancers: A Meta-Analysis. Medicine (Baltimore) 2019, 98, e17346.
  34. Kostecka, L.G.; Olseen, A.; Kang, K.; Torga, G.; Pienta, K.J.; Amend, S.R. High KIFC1 Expression Is Associated with Poor Prognosis in Prostate Cancer. Med. Oncol. 2021, 38, 47.
  35. Pannu, V.; Rida, P.C.; Ogden, A.; Turaga, R.C.; Donthamsetty, S.; Bowen, N.J.; Rudd, K.; Gupta, M.V.; Reid, M.D.; Cantuaria, G.; et al. HSET Overexpression Fuels Tumor Progression Via Centrosome Clustering-Independent Mechanisms in Breast Cancer Patients. Oncotarget 2015, 6, 6076–6091.
  36. Li, Y.; Lu, W.; Chen, D.; Boohaker, R.J.; Zhai, L.; Padmalayam, I.; Wennerberg, K.; Xu, B.; Zhang, W. KIFC1 Is a Novel Potential Therapeutic Target for Breast Cancer. Cancer Biol. Ther. 2015, 16, 1316–1322.
  37. Xiao, Y.X.; Yang, W.X. KIFC1: A Promising Chemotherapy Target for Cancer Treatment? Oncotarget 2016, 7, 48656–48670.
  38. Khodjakov, A.; Rieder, C.L. Centrosomes Enhance the Fidelity of Cytokinesis in Vertebrates and Are Required for Cell Cycle Progression. J. Cell Biol. 2001, 153, 237–242.
  39. Piel, M.; Nordberg, J.; Euteneuer, U.; Bornens, M. Centrosome-Dependent Exit of Cytokinesis in Animal Cells. Science 2001, 291, 1550–1553.
  40. Zyss, D.; Gergely, F. Centrosome Function in Cancer: Guilty or Innocent? Trends Cell Biol. 2009, 19, 334–346.
  41. Sabat-Pospiech, D.; Fabian-Kolpanowicz, K.; Prior, I.A.; Coulson, J.M.; Fielding, A.B. Targeting Centrosome Amplification, an Achilles’ Heel of Cancer. Biochem. Soc. Trans. 2019, 47, 1209–1222.
  42. Vakifahmetoglu, H.; Olsson, M.; Zhivotovsky, B. Death through a Tragedy: Mitotic Catastrophe. Cell Death Differ. 2008, 15, 1153–1162.
  43. Braun, M.; Lansky, Z.; Bajer, S.; Fink, G.; Kasprzak, A.A.; Diez, S. The Human Kinesin-14 HSET Tracks the Tips of Growing Microtubules in vitro. Cytoskeleton 2013, 70, 515–521.
  44. Kleylein-Sohn, J.; Pollinger, B.; Ohmer, M.; Hofmann, F.; Nigg, E.A.; Hemmings, B.A.; Wartmann, M. Acentrosomal Spindle Organization Renders Cancer Cells Dependent on the Kinesin HSET. J. Cell Sci. 2012, 125, 5391–5402.
  45. Ganem, N.J.; Godinho, S.A.; Pellman, D. A Mechanism Linking Extra Centrosomes to Chromosomal Instability. Nature 2009, 460, 278–282.
  46. Silkworth, W.T.; Nardi, I.K.; Scholl, L.M.; Cimini, D. Multipolar Spindle Pole Coalescence Is a Major Source of Kinetochore Mis-Attachment and Chromosome Mis-Segregation in Cancer Cells. PLoS ONE 2009, 4, e6564.
  47. Levine, M.S.; Holland, A.J. The Impact of Mitotic Errors on Cell Proliferation and Tumorigenesis. Genes. Dev. 2018, 32, 620–638.
  48. Jusino, S.; Fernandez-Padin, F.M.; Saavedra, H.I. Centrosome Aberrations and Chromosome Instability Contribute to Tumorigenesis and Intra-Tumor Heterogeneity. J. Cancer Metastasis. Treat. 2018, 4, 43.
  49. McDermott, K.M.; Zhang, J.; Holst, C.R.; Kozakiewicz, B.K.; Singla, V.; Tlsty, T.D. p16(INK4a) Prevents Centrosome Dysfunction and Genomic Instability in Primary Cells. PLoS Biol. 2006, 4, e51.
  50. Dominguez, D.; Feijoo, P.; Bernal, A.; Ercilla, A.; Agell, N.; Genesca, A.; Tusell, L. Centrosome Aberrations in Human Mammary Epithelial Cells Driven by Cooperative Interactions between p16INK4a Deficiency and Telomere-Dependent Genotoxic Stress. Oncotarget 2015, 6, 28238–28256.
  51. Stearns, T. Centrosome Duplication. a Centriolar Pas De Deux. Cell 2001, 105, 417–420.
  52. Giacinti, C.; Giordano, A. RB and Cell Cycle Progression. Oncogene 2006, 25, 5220–5227.
  53. Iovino, F.; Lentini, L.; Amato, A.; Di Leonardo, A. RB Acute Loss Induces Centrosome Amplification and Aneuploidy in Murine Primary Fibroblasts. Mol. Cancer 2006, 5, 38.
  54. Fukasawa, K.; Choi, T.; Kuriyama, R.; Rulong, S.; Vande Woude, G.F. Abnormal Centrosome Amplification in the Absence of p53. Science 1996, 271, 1744–1747.
  55. Markey, M.P.; Bergseid, J.; Bosco, E.E.; Stengel, K.; Xu, H.; Mayhew, C.N.; Schwemberger, S.J.; Braden, W.A.; Jiang, Y.; Babcock, G.F.; et al. Loss of the Retinoblastoma Tumor Suppressor: Differential Action on Transcriptional Programs Related to Cell Cycle Control and Immune Function. Oncogene 2007, 26, 6307–6318.
  56. Mittal, K.; Wei, G.; Kaur, J.; Choi, D.H.; Reid, M.D.; Rida, P.C.G.; Aneja, R. KIFC1 as a Novel Therapeutic Target for p53 Mutant Colorectal Cancer. J. Clin. Oncol. 2018, 36, e15585.
  57. Kim, N.; Song, K. KIFC1 Is Essential for Bipolar Spindle Formation and Genomic Stability in the Primary Human Fibroblast IMR-90 Cell. Cell Struct. Funct. 2013, 38, 21–30.
  58. Malorni, L.; Piazza, S.; Ciani, Y.; Guarducci, C.; Bonechi, M.; Biagioni, C.; Hart, C.D.; Verardo, R.; Di Leo, A.; Migliaccio, I. A Gene Expression Signature of Retinoblastoma Loss-of-Function Is a Predictive Biomarker of Resistance to Palbociclib in Breast Cancer Cell Lines and Is Prognostic in Patients with ER Positive Early Breast Cancer. Oncotarget 2016, 7, 68012–68022.
  59. Lee, J.K.; Garbe, J.C.; Vrba, L.; Miyano, M.; Futscher, B.W.; Stampfer, M.R.; LaBarge, M.A. Age and the Means of by Passing Stasis Influence the Intrinsic Subtype of Immortalized Human Mammary Epithelial Cells. Front. Cell Dev. Biol. 2015, 3, 13.
  60. Tusell, L.; Pampalona, J.; Soler, D.; Frias, C.; Genesca, A. Different Outcomes of Telomere-Dependent Anaphase Bridges. Biochem. Soc. Trans. 2010, 38, 1698–1703.
  61. Tanaka, H.; Abe, S.; Huda, N.; Tu, L.; Beam, M.J.; Grimes, B.; Gilley, D. Telomere Fusions in Early Human Breast Carcinoma. Proc. Natl. Acad. Sci. USA 2012, 109, 14098–14103.
  62. Gao, Y.; Zhang, B. Expression of TEIF Protein in Colorectal Tumors and Its Correlation with Centrosome Abnormality. Ai Zheng 2009, 28, 1277–1282.
  63. Fan, G.; Sun, L.; Meng, L.; Hu, C.; Wang, X.; Shi, Z.; Hu, C.; Han, Y.; Yang, Q.; Cao, L.; et al. The ATM and ATR Kinases Regulate Centrosome Clustering and Tumor Recurrence by Targeting KIFC1 Phosphorylation. Nat. Commun. 2021, 12, 20.
  64. Stampfer, M.R.; LaBarge, M.A.; Garbe, J.C. An Integrated Human Mammary Epithelial Cell Culture System for Studying Carcinogenesis and Aging. In Cell and Molecular Biology of Breast Cancer; Humana Press: Totowa, NJ, USA, 2013; pp. 323–361.
  65. Zeng, X.; Shaikh, F.Y.; Harrison, M.K.; Adon, A.M.; Trimboli, A.J.; Carroll, K.A.; Sharma, N.; Timmers, C.; Chodosh, L.A.; Leone, G.; et al. The Ras Oncogene Signals Centrosome Amplification in Mammary Epithelial Cells through Cyclin D1/Cdk4 and Nek2. Oncogene 2010, 29, 5103–5112.
  66. Brabletz, T.; Kalluri, R.; Nieto, M.A.; Weinberg, R.A. EMT in Cancer. Nat. Rev. Cancer 2018, 18, 128–134.
  67. Rhys, A.D.; Monteiro, P.; Smith, C.; Vaghela, M.; Arnandis, T.; Kato, T.; Leitinger, B.; Sahai, E.; McAinsh, A.; Charras, G.; et al. Loss of E-Cadherin Provides Tolerance to Centrosome Amplification in Epithelial Cancer Cells. J. Cell Biol. 2018, 217, 195–209.
  68. Li, J.; Diao, H.; Guan, X.; Tian, X. Kinesin Family Member C1 (KIFC1) Regulated by Centrosome Protein E (CENPE) Promotes Proliferation, Migration, and Epithelial-Mesenchymal Transition of Ovarian Cancer. Med. Sci. Monit. 2020, 26, e927869.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Cell Biology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Nikita Wright
View Times: 294
Revisions: 2 times (View History)
Update Date: 07 Jan 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback