Pathogenetic Basis of Pleural Mesothelioma: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Francesco Rocco Bertuccio
,
Francesco Agustoni
,
Giulia Galli
,
Chandra Bortolotto
,
Jessica Saddi
,
Guido Baietto
,
Nicola Baio
,
Simone Montini
,
Paola Putignano
,
Gioacchino D’Ambrosio
,
Angelo G. Corsico
,
Paolo Pedrazzoli
,
Giulia Maria Stella

Pleural mesothelioma (PM) is a particularly aggressive cancer arising from mesothelial cells lining the thoracic (pleura) cavity whose development has been related to the exposure to carcinogenic biopersistent mineral fibers, mainly asbestos. Pleural mesothelioma is an aggressive disease with diffuse nature, low median survival, and prolonged latency presenting difficulty in prognosis, diagnosis, and treatment. 

  • pleural mesothelioma
  • asbestos
  • mineral fibers
  • genetic
  • carcinogenesis

1. Introduction

Pleural mesothelioma (PM) is a particularly aggressive cancer arising from mesothelial cells lining the thoracic (pleura) cavity whose development has been related to the exposure to carcinogenic biopersistent mineral fibers, mainly asbestos [1]. The disease is characterized by heterogeneity, intended at several levels, which is ultimately responsible for the limited response to therapies and poor patient survival [2]. However, the advent of novel biotechnologies and next-generation approaches has also allowed for the identification of treatable traits with the development of targeted approaches for the otherwise neglected pathology.
It is uncertain how common PM is worldwide. Driscoll et al. calculated that up to 43,000 persons per year die from the illness worldwide [3]. Although the use of asbestos is officially prohibited in 67 countries, Australia, Japan, North America, and western Europe together are thought to account for about 10,000 cases of mesothelioma each year [4]. With a median diagnostic age of 76 years, mesothelioma is a disease primarily affecting the elderly [5]. It is uncommon before the age of 50, but its frequency rises abruptly beyond that [5]. World-standardized incidence rates per 100,000 persons are 0.7 and 0.3 in the United States and 1.7 and 0.4 in Europe (for males and females, respectively). The Netherlands, the United Kingdom, and Australia are among the nations with the highest incidence of asbestos use in the past [6]. Along with relatively recent usage bans and a 40-year latency between exposure and presentation, incidence is still rising in many countries. Early in the new millennium, mesothelioma rates in Europe were rapidly increasing; nevertheless, due to the widespread home use of asbestos, the frequency of this disease is uncertain in the long run. Furthermore, the usage of asbestos is still growing in developing nations. Males are more likely than females to contract the disease, and females are claimed to have a higher rate of survival in several studies [7]. The World Health Organization (WHO) has identified PM as a very uncommon tumor that is directly linked to all forms of asbestos exposure, making it a preventable and industrial cancer. Compared to Europe, Central Asia still has a high rate of asbestos use, and some nations—including the US—only have usage limitations rather than outright bans [8].

2. The Role of Asbestos

Due to its low cost-effectiveness and insulating qualities, asbestos has been widely used since the middle of the 20th century. Since the last decade of the 20th century, asbestos use has been strictly regulated in the United States and banned in Europe and Australia due to in vivo evidence of its carcinogenic potential [9]. The word “asbestos” is used in national regulatory papers to refer to six commercially exploited minerals: one serpentine (chrysotile) and five amphiboles (crocidolite, actinolite, tremolite, anthophyllite, and amosite). On the other hand, about 400 other minerals with comparable chemical and physical characteristics are found in the natural environment; their usage is uncontrolled, and they are not subject to regulations. Moreover, naturally occurring erionite fibers, which are even more carcinogenic than asbestos, have been utilized for building and road paving materials, and residents of some Cappadocian villages in Turkey and in some areas of North Dakota (US) are exposed to these fibers [10][11]. It is now commonly known that specific mineral fiber types have different carcinogenic potencies depending on their size, durability, dose, and physical characteristics [12][13][14]. Thin, long fibers have been linked to increased mutagenic and cytotoxic efficacy [15] due to the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in response to “frustrated phagocytosis” [16][17][18]. However, due to its significantly lower inflammatory response when compared to carcinogenic fibers, palygorskite—a fiber that is highly prevalent in southern Nevada—was unable to promote cancer in vivo while having lower in vitro cytotoxicity and biopersistence [19]. The mechanisms underlying asbestos carcinogenesis have long been enigmatic [20][21]. However, mesothelial cells undergo an equivalent transformation under extended contact to chrysotile fibers [17][18]. Furthermore, it has been demonstrated that ROS released by asbestos-activated macrophages may indirectly cause DNA damage by forming 8-hydroxy-2′-deoxyguanosine (8-OHdG) adducts [22]. According to recent research on iron-catalyzed ROS production, asbestos-related carcinogenesis may entail ferroptosis, a non-apoptotic, iron-dependent cell death mechanism [23]. Furthermore, through stimulation of the PI3K/MEK5/Fra-1 axis, hepatocyte growth factor (HGF) has been implicated in asbestos-induced carcinogenesis [24]. However, human mesothelial cells (HM), a kind of cell that is especially vulnerable to fiber cytotoxicity and was previously thought to be apoptotic, die when exposed to asbestos particles [25]. Later, it was evident that tumor necrosis factor-alpha (TNF-α), an inflammatory mediator, was linked to the pathogenesis of asbestos [26]. One of the main contributing factors to the pathophysiology and carcinogenesis caused by asbestos and other mineral fibers known to cause cancer is chronic inflammation. The pro-inflammatory milieu created at the fiber deposition site by macrophages and PM, along with the biopersistence of many mineral fibers, enables the avoidance of cell death and ultimately leads to neoplastic transformation [27][28]. The passive release of high mobility group box 1 (HMGB1) by necrotic PM at the location of fiber deposition characterizes this controlled form of necrosis. One such damage-associated molecular protein (DAMP) is HMGB1, which encourages the macrophage recruitment necessary to maintain the chronic inflammatory process. To prime macrophages for inflammasome activation, HMGB1 binds to RAGE and other HMGB1 receptors. This, in conjunction with other stimuli, such as endogenous ROS produced following asbestos exposure, causes the NLRP3 inflammasome to assemble through the oligomerization of inactive NLRP3, apoptosis-associated speck-like protein (ASC), and procaspase-1. IL-1β, IL-18, IL-1α, and HMGB1 are released when the NLRP3 inflammasome is activated, initiating an autocrine chronic inflammatory process [29][30]. Additionally, TNF-α is secreted during this process, which stimulates NF-κB and increases HM’s chance of survival after asbestos exposure. Mesothelioma occurs because of the surviving HM’s continued proliferation and accumulation of genetic alterations. Furthermore, it was observed that ethyl pyruvate, which has been identified as an efficient HMGB1 inhibitor and suppressor of RAGE receptor expression, decreased the proliferation of mesothelioma cells both in vitro and in vivo. Both actions help to lower the malignancy of mesothelioma [31]. Whereas HMGB1 is primarily identified in the nucleus of HM, it has also been detected in the cytoplasm and nucleus of mesothelioma. HMGB1 is actively secreted into the extracellular space during mesothelioma, where it binds to RAGE and TLR receptors to form an autocrine pathway that stimulates the growth, motility, and survival of the cancerous cells [32].

3. Genetic Basis of the Disease

As not all PM patients have a history of asbestos exposure, asbestos fibers primarily cause mortality by necrosis and, to a lesser extent, through other cell death processes. Somatic gene mutations that impact DNA repair processes are frequently linked to carcinogenesis, as they cause an increase in the fraction of cells with damaged DNA and the accumulation of damage to DNA. Cancer may arise when these cells develop survival mechanisms like to those triggered by the HMGB1 pathway in mesothelioma. Inherited mutations that impact DNA repair and other genes may exacerbate the carcinogenesis process by making an individual more vulnerable to environmental carcinogens [33][34]. The present method used to investigate GxE interactions in the realm of carcinogens combines genetics (G) and environmental (E) investigations. Recently, the increase in the level of mutations in the genome of cancer cells has been linked to the catastrophic event known as chromothripsis. A single, segregated chromosome that is randomly reassembled can break, resulting in chromothripsis, which causes erroneous rearrangements or deletions of DNA sequences. As a result, huge genomic changes could happen after just one chromothripsis event. This elevated mutational status ultimately promotes carcinogenesis by favoring oncogene activations or the loss of tumor suppressor activities [35]. Notably, noncontiguous biallelic genome alterations with the characteristic pattern of chromothripsis and associated with possible neoantigen expression were found in genomic studies of mesothelioma cells and specimens. These findings may have intriguing implications for the immunogenicity of mesothelioma [36][37][38]. Mutations were discovered in several tumor suppressors connected to apoptosis and cell cycle regulation in human mesothelioma. The homozygous deletion on locus 9p21, which impacts the transcription of two tumor suppressors—p16INK4a and p14ARF—is one of the main genetic abnormalities seen in mesothelioma [39]. By attaching to CDK4 and CDK6, P16INK4a prevents cell proliferation, and p14 encourages apoptosis by preventing p53 ubiquitylation. Up to 80% of primary pleural mesotheliomas lacked p16, according to cytogenetic research, and p16 inactivation is associated with a worse prognosis [40]. Transgenic p14 (+/−) mice showed decreased heterogeneity for p14 in their extracted primary mouse tumors, and these mice were more prone to asbestos-induced carcinogenesis [41]. Mesothelioma also exhibits significant mutations in Hippo signaling pathway intermediates. In almost 40% of cases of malignant mesothelioma, the upstream initiator of Hippo, neurofibromatosis type 2 (NF2)/Merlin, is inactive [42]. Remarkably, after BRCA1-related protein-1, NF2 is the second most often mutated gene in mesothelioma (BAP1). Compared to wildtype controls, heterozygous NF2 (+/−) mice showed an accelerated carcinogenesis and were more susceptible to asbestos exposure [43]. In the Hippo pathway, nonfunctional NF2 causes nuclear accumulation of WW Domain-contain transcription regulator (WWTR1 or TAZ) and yes-associated protein (YAP). One effect of the pro-inflammatory milieu created by asbestos fiber exposure is the increased nucleus formation of the YAP/TAZ complex, which, in turn, stimulates the expression of several proto-oncogenes and supports the survival of cancer cells [44]. It was feasible to identify potential frequent abnormalities at chromosome 3p21 in two unrelated US families with a high incidence of mesothelioma and no occupational asbestos exposure as a result of linkage analysis and array-comparative genomic hybridization (aCGH). Following sequencing, germline BAP1 mutations linked to autosomal dominant transmission of uveal melanoma and mesothelioma were discovered [45][46]. The BAP1-related cancer syndrome was discovered in individuals with germline altered BAP1 prone to additional cancer forms such renal cell carcinoma and squamous cell carcinoma [45][47][48]. According to recent research, BAP1 has multiple activities in the cytoplasm and nucleus that work together to prevent tumor growth. The endoplasmic reticulum (ER) fraction is the primary location of cytoplasmic BAP1, where it deubiquitylates and stabilizes the type 3 inositol-1,4,5-trisphosphate receptor (IP3R3). Via the mitochondrial uniporter channel (MUC) in the inner mitochondrial membrane and the voltage-dependent anion channels (VDACs) in the outer mitochondrial membrane, IP3R3 facilitates the release of Ca2+ from the ER into the mitochondrial space. The release of cytochrome c, which triggers apoptosis, is caused by an increase in Ca2+ concentration in the mitochondria. Reduced BAP1 dosage affects both DNA repair, accumulated DNA damage, and the apoptotic response in heterozygous BAP1+/− circumstances, such as in individuals in the families with the BAP1 cancer syndrome. This double function both favorably selects cells with cancer-causing mutations and encourages the growth of tumors [46]. The delineation of the intricate web of molecular processes mediated by asbestos carcinogenesis was aided by the discovery of BAP1 as a primary regulator of metabolism and cell death [48]. To fully understand the role of the genes predisposing to mesothelioma in the molecular pathways of asbestos carcinogenesis, more research will be necessary.

This entry is adapted from the peer-reviewed paper 10.3390/cancers15245731

References

  1. Gaudino, G.; Xue, J.; Yang, H. How Asbestos and Other Fibers Cause Mesothelioma. Transl. Lung Cancer Res. 2020, 9, S39–S46.
  2. Abbott, D.M.; Bortolotto, C.; Benvenuti, S.; Lancia, A.; Filippi, A.R.; Stella, G.M. Malignant Pleural Mesothelioma: Genetic and Microenviromental Heterogeneity as an Unexpected Reading Frame and Therapeutic Challenge. Cancers 2020, 12, 1186.
  3. Driscoll, T.; Nelson, D.I.; Steenland, K.; Leigh, J.; Concha-Barrientos, M.; Fingerhut, M.; Prüss-Ustün, A. The Global Burden of Disease Due to Occupational Carcinogens. Am. J. Ind. Med. 2005, 48, 419–431.
  4. Delgermaa, V.; Takahashi, K.; Park, E.K.; Le, G.V.; Hara, T.; Sorahan, T. Les Décés Mondiaux Par Mésothéliome Rapportés á l’Organisation Mondiale de La Santé Entre 1994 et 2008. Bull. World Health Organ. 2011, 89, 716–724.
  5. Popat, S.; Baas, P.; Faivre-Finn, C.; Girard, N.; Nicholson, A.G.; Nowak, A.K.; Opitz, I.; Scherpereel, A.; Reck, M. Malignant Pleural Mesothelioma: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up☆. Ann. Oncol. 2022, 33, 129–142.
  6. Alpert, N.; van Gerwen, M.; Taioli, E. Epidemiology of Mesothelioma in the 21st Century in Europe and the United States, 40 Years after Restricted/Banned Asbestos Use. Transl. Lung Cancer Res. 2020, 9, S28–S38.
  7. Jiang, Z.; Chen, T.; Chen, J.; Ying, S.; Gao, Z.; He, X.; Miao, C.; Yu, M.; Feng, L.; Xia, H.; et al. Hand-Spinning Chrysotile Exposure and Risk of Malignant Mesothelioma: A Case–Control Study in Southeastern China. Int. J. Cancer 2018, 142, 514–523.
  8. Schumann, S.O.; Kocher, G.; Minervini, F. Epidemiology, Diagnosis and Treatment of the Malignant Pleural Mesothelioma, a Narrative Review of Literature. J. Thorac. Dis. 2021, 13, 2510–2523.
  9. Cohen-Mansfield, J.; Dakheel-Ali, M.; Marx, M.S.; Thein, K.; Regier, N.G.; Waage, P. HHS Public Access. Physiol. Behav. 2017, 176, 139–148.
  10. Baumann, F.; Ambrosi, J.-P.; Carbone, M. Asbestos Is Not Just Asbestos: An Unrecognised Health Hazard. Lancet. Oncol. 2013, 14, 576–578.
  11. Carbone, M.; Emri, S.; Dogan, A.U.; Steele, I.; Tuncer, M.; Pass, H.I.; Baris, Y.I. A Mesothelioma Epidemic in Cappadocia: Scientific Developments and Unexpected Social Outcomes. Nat. Rev. Cancer 2007, 7, 147–154.
  12. Stanton, M.F.; Laynard, M.; Tegeris, A.; Miller, E.; May, M.; Kent, E. Carcinogenicity of Fibrous Glass: Pleural Response in the Rat in Relation to Fiber Dimension. J. Natl. Cancer Inst. 1977, 58, 587–603.
  13. Huang, S.X.L.; Jaurand, M.-C.; Kamp, D.W.; Whysner, J.; Hei, T.K. Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases. J. Toxicol. Environ. Health. B Crit. Rev. 2011, 14, 179–245.
  14. Mossman, B.T. In Vitro Studies on the Biologic Effects of Fibers: Correlation with in Vivo Bioassays. Environ. Health Perspect. 1990, 88, 319–322.
  15. Barlow, C.A.; Grespin, M.; Best, E.A. Asbestos Fiber Length and Its Relation to Disease Risk. Inhal. Toxicol. 2017, 29, 541–554.
  16. Carbone, M.; Yang, H. Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma. Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res. 2012, 18, 598–604.
  17. Bernstein, D.M.; Donaldson, K.; Decker, U.; Gaering, S.; Kunzendorf, P.; Chevalier, J.; Holm, S.E. A Biopersistence Study Following Exposure to Chrysotile Asbestos Alone or in Combination with Fine Particles. Inhal. Toxicol. 2008, 20, 1009–1028.
  18. Qi, F.; Okimoto, G.; Jube, S.; Napolitano, A.; Pass, H.I.; Laczko, R.; Demay, R.M.; Khan, G.; Tiirikainen, M.; Rinaudo, C.; et al. Continuous Exposure to Chrysotile Asbestos Can Cause Transformation of Human Mesothelial Cells via HMGB1 and TNF-α Signaling. Am. J. Pathol. 2013, 183, 1654–1666.
  19. Larson, D.; Powers, A.; Ambrosi, J.-P.; Tanji, M.; Napolitano, A.; Flores, E.G.; Baumann, F.; Pellegrini, L.; Jennings, C.J.; Buck, B.J.; et al. Investigating Palygorskite’s Role in the Development of Mesothelioma in Southern Nevada: Insights into Fiber-Induced Carcinogenicity. J. Toxicol. Environ. Health. B Crit. Rev. 2016, 19, 213–230.
  20. Carbone, M.; Adusumilli, P.S.; Alexander, H.R.J.; Baas, P.; Bardelli, F.; Bononi, A.; Bueno, R.; Felley-Bosco, E.; Galateau-Salle, F.; Jablons, D.; et al. Mesothelioma: Scientific Clues for Prevention, Diagnosis, and Therapy. CA. Cancer J. Clin. 2019, 69, 402–429.
  21. Nagai, H.; Ishihara, T.; Lee, W.-H.; Ohara, H.; Okazaki, Y.; Okawa, K.; Toyokuni, S. Asbestos Surface Provides a Niche for Oxidative Modification. Cancer Sci. 2011, 102, 2118–2125.
  22. Xu, A.; Wu, L.J.; Santella, R.M.; Hei, T.K. Role of Oxyradicals in Mutagenicity and DNA Damage Induced by Crocidolite Asbestos in Mammalian Cells. Cancer Res. 1999, 59, 5922–5926.
  23. Toyokuni, S. Iron Addiction with Ferroptosis-Resistance in Asbestos-Induced Mesothelial Carcinogenesis: Toward the Era of Mesothelioma Prevention. Free Radic. Biol. Med. 2019, 133, 206–215.
  24. Ramos-Nino, M.E.; Blumen, S.R.; Sabo-Attwood, T.; Pass, H.; Carbone, M.; Testa, J.R.; Altomare, D.A.; Mossman, B.T. HGF Mediates Cell Proliferation of Human Mesothelioma Cells through a PI3K/MEK5/Fra-1 Pathway. Am. J. Respir. Cell Mol. Biol. 2008, 38, 209–217.
  25. Broaddus, V.C.; Yang, L.; Scavo, L.M.; Ernst, J.D.; Boylan, A.M. Asbestos Induces Apoptosis of Human and Rabbit Pleural Mesothelial Cells via Reactive Oxygen Species. J. Clin. Investig. 1996, 98, 2050–2059.
  26. Yang, H.; Bocchetta, M.; Kroczynska, B.; Elmishad, A.G.; Chen, Y.; Liu, Z.; Bubici, C.; Mossman, B.T.; Pass, H.I.; Testa, J.R.; et al. TNF-Alpha Inhibits Asbestos-Induced Cytotoxicity via a NF-KappaB-Dependent Pathway, a Possible Mechanism for Asbestos-Induced Oncogenesis. Proc. Natl. Acad. Sci. USA 2006, 103, 10397–10402.
  27. Carbone, M.; Yang, H. Mesothelioma: Recent Highlights. Ann. Transl. Med. 2017, 5, 238.
  28. Yang, H.; Rivera, Z.; Jube, S.; Nasu, M.; Bertino, P.; Goparaju, C.; Franzoso, G.; Lotze, M.T.; Krausz, T.; Pass, H.I.; et al. Programmed Necrosis Induced by Asbestos in Human Mesothelial Cells Causes High-Mobility Group Box 1 Protein Release and Resultant Inflammation. Proc. Natl. Acad. Sci. USA 2010, 107, 12611–12616.
  29. Kadariya, Y.; Menges, C.W.; Talarchek, J.; Cai, K.Q.; Klein-Szanto, A.J.; Pietrofesa, R.A.; Christofidou-Solomidou, M.; Cheung, M.; Mossman, B.T.; Shukla, A.; et al. Inflammation-Related IL1β/IL1R Signaling Promotes the Development of Asbestos-Induced Malignant Mesothelioma. Cancer Prev. Res. 2016, 9, 406–414.
  30. Thompson, J.K.; Shukla, A.; Leggett, A.L.; Munson, P.B.; Miller, J.M.; MacPherson, M.B.; Beuschel, S.L.; Pass, H.I.; Shukla, A. Extracellular Signal Regulated Kinase 5 and Inflammasome in Progression of Mesothelioma. Oncotarget 2018, 9, 293–305.
  31. Pellegrini, L.; Xue, J.; Larson, D.; Pastorino, S.; Jube, S.; Forest, K.H.; Saad-Jube, Z.S.; Napolitano, A.; Pagano, I.; Negi, V.S.; et al. HMGB1 Targeting by Ethyl Pyruvate Suppresses Malignant Phenotype of Human Mesothelioma. Oncotarget 2017, 8, 22649–22661.
  32. Jube, S.; Rivera, Z.S.; Bianchi, M.E.; Powers, A.; Wang, E.; Pagano, I.; Pass, H.I.; Gaudino, G.; Carbone, M.; Yang, H. Cancer Cell Secretion of the DAMP Protein HMGB1 Supports Progression in Malignant Mesothelioma. Cancer Res. 2012, 72, 3290–3301.
  33. Affar, E.B.; Carbone, M. BAP1 Regulates Different Mechanisms of Cell Death. Cell Death Dis. 2018, 9, 1151.
  34. Carbone, M.; Amelio, I.; Affar, E.B.; Brugarolas, J.; Cannon-Albright, L.A.; Cantley, L.C.; Cavenee, W.K.; Chen, Z.; Croce, C.M.; Andrea, A.D.; et al. Consensus Report of the 8 and 9th Weinman Symposia on Gene x Environment Interaction in Carcinogenesis: Novel Opportunities for Precision Medicine. Cell Death Differ. 2018, 25, 1885–1904.
  35. Ly, P.; Cleveland, D.W. Rebuilding Chromosomes After Catastrophe: Emerging Mechanisms of Chromothripsis. Trends Cell Biol. 2017, 27, 917–930.
  36. Yoshikawa, Y.; Emi, M.; Hashimoto-Tamaoki, T.; Ohmuraya, M.; Sato, A.; Tsujimura, T.; Hasegawa, S.; Nakano, T.; Nasu, M.; Pastorino, S.; et al. High-Density Array-CGH with Targeted NGS Unmask Multiple Noncontiguous Minute Deletions on Chromosome 3p21 in Mesothelioma. Proc. Natl. Acad. Sci. USA 2016, 113, 13432–13437.
  37. Oey, H.; Daniels, M.; Relan, V.; Chee, T.M.; Davidson, M.R.; Yang, I.A.; Ellis, J.J.; Fong, K.M.; Krause, L.; Bowman, R. V Whole-Genome Sequencing of Human Malignant Mesothelioma Tumours and Cell Lines. Carcinogenesis 2019, 40, 724–734.
  38. Mansfield, A.S.; Peikert, T.; Smadbeck, J.B.; Udell, J.B.M.; Garcia-Rivera, E.; Elsbernd, L.; Erskine, C.L.; Van Keulen, V.P.; Kosari, F.; Murphy, S.J.; et al. Neoantigenic Potential of Complex Chromosomal Rearrangements in Mesothelioma. J. Thorac. Oncol. Off. Publ. Int. Assoc. Study Lung Cancer 2019, 14, 276–287.
  39. Husain, A.N.; Colby, T.V.; Ordóñez, N.G.; Allen, T.C.; Attanoos, R.L.; Beasley, M.B.; Butnor, K.J.; Chirieac, L.R.; Churg, A.M.; Dacic, S.; et al. Guidelines for Pathologic Diagnosis of Malignant Mesothelioma 2017 Update of the Consensus Statement From the International Mesothelioma Interest Group. Arch. Pathol. Lab. Med. 2018, 142, 89–108.
  40. Jongsma, J.; van Montfort, E.; Vooijs, M.; Zevenhoven, J.; Krimpenfort, P.; van der Valk, M.; van de Vijver, M.; Berns, A. A Conditional Mouse Model for Malignant Mesothelioma. Cancer Cell 2008, 13, 261–271.
  41. Altomare, D.A.; Menges, C.W.; Pei, J.; Zhang, L.; Skele-Stump, K.L.; Carbone, M.; Kane, A.B.; Testa, J.R. Activated TNF-Alpha/NF-KappaB Signaling via down-Regulation of Fas-Associated Factor 1 in Asbestos-Induced Mesotheliomas from Arf Knockout Mice. Proc. Natl. Acad. Sci. USA 2009, 106, 3420–3425.
  42. Sato, T.; Sekido, Y. NF2/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma. Int. J. Mol. Sci. 2018, 19, 988.
  43. Altomare, D.A.; Vaslet, C.A.; Skele, K.L.; De Rienzo, A.; Devarajan, K.; Jhanwar, S.C.; McClatchey, A.I.; Kane, A.B.; Testa, J.R. A Mouse Model Recapitulating Molecular Features of Human Mesothelioma. Cancer Res. 2005, 65, 8090–8095.
  44. Rehrauer, H.; Wu, L.; Blum, W.; Pecze, L.; Henzi, T.; Serre-Beinier, V.; Aquino, C.; Vrugt, B.; de Perrot, M.; Schwaller, B.; et al. How Asbestos Drives the Tissue towards Tumors: YAP Activation, Macrophage and Mesothelial Precursor Recruitment, RNA Editing, and Somatic Mutations. Oncogene 2018, 37, 2645–2659.
  45. Wiesner, T.; Obenauf, A.C.; Murali, R.; Fried, I.; Griewank, K.G.; Ulz, P.; Windpassinger, C.; Wackernagel, W.; Loy, S.; Wolf, I.; et al. Germline Mutations in BAP1 Predispose to Melanocytic Tumors. Nat. Genet. 2011, 43, 1018–1021.
  46. Bononi, A.; Giorgi, C.; Patergnani, S.; Larson, D.; Verbruggen, K.; Tanji, M.; Pellegrini, L.; Signorato, V.; Olivetto, F.; Pastorino, S.; et al. BAP1 Regulates IP3R3-Mediated Ca(2+) Flux to Mitochondria Suppressing Cell Transformation. Nature 2017, 546, 549–553.
  47. Testa, J.R.; Cheung, M.; Pei, J.; Below, J.E.; Tan, Y.; Sementino, E.; Cox, N.J.; Dogan, A.U.; Pass, H.I.; Trusa, S.; et al. Germline BAP1 Mutations Predispose to Malignant Mesothelioma. Nat. Genet. 2011, 43, 1022–1025.
  48. Bononi, A.; Yang, H.; Giorgi, C.; Patergnani, S.; Pellegrini, L.; Su, M.; Xie, G.; Signorato, V.; Pastorino, S.; Morris, P.; et al. Germline BAP1 Mutations Induce a Warburg Effect. Cell Death Differ. 2017, 24, 1694–1704.
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.
This entry is offline, you can click here to edit this entry!
Video Production Service
Feedback