Perspective: The Mechanobiology of Hepatocellular Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. The Liver Progressively Stiffens in Fibrosis and Cirrhosis
3. Liver Cells Are Mechanosensitive
4. Mechanically Induced Nuclear Deformation Activates Oncogenic Signaling and Increases DNA Damage
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- McGlynn, K.A.; Petrick, J.L.; El-Serag, H.B. Epidemiology of Hepatocellular Carcinoma. Hepatology 2021, 73 (Suppl. 1), 4–13. [Google Scholar] [CrossRef] [PubMed]
- Zhang, D.Y.; Friedman, S.L. Fibrosis-dependent mechanisms of hepatocarcinogenesis. Hepatology 2012, 56, 769–775. [Google Scholar] [CrossRef] [PubMed]
- Nahon, P.; Kettaneh, A.; Lemoine, M.; Seror, O.; Barget, N.; Trinchet, J.C.; Beaugrand, M.; Ganne-Carrie, N. Liver stiffness measurement in patients with cirrhosis and hepatocellular carcinoma: A case-control study. Eur. J. Gastroenterol. Hepatol. 2009, 21, 214–219. [Google Scholar] [CrossRef] [PubMed]
- Tatsumi, A.; Maekawa, S.; Sato, M.; Komatsu, N.; Miura, M.; Amemiya, F.; Nakayama, Y.; Inoue, T.; Sakamoto, M.; Enomoto, N. Liver stiffness measurement for risk assessment of hepatocellular carcinoma. Hepatol. Res. 2015, 45, 523–532. [Google Scholar] [CrossRef]
- Singh, S.; Fujii, L.L.; Murad, M.H.; Wang, Z.; Asrani, S.K.; Ehman, R.L.; Kamath, P.S.; Talwalkar, J.A. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: A systematic review and meta-analysis. Clin. Gastroenterol. Hepatol. 2013, 11, 1573–1584. [Google Scholar] [CrossRef] [Green Version]
- Cescon, M.; Colecchia, A.; Cucchetti, A.; Peri, E.; Montrone, L.; Ercolani, G.; Festi, D.; Pinna, A.D. Value of transient elastography measured with FibroScan in predicting the outcome of hepatic resection for hepatocellular carcinoma. Ann. Surg. 2012, 256, 706–712. [Google Scholar] [CrossRef]
- You, J.; Park, S.A.; Shin, D.S.; Patel, D.; Raghunathan, V.K.; Kim, M.; Murphy, C.J.; Tae, G.; Revzin, A. Characterizing the effects of heparin gel stiffness on function of primary hepatocytes. Tissue Eng. Part A 2013, 19, 2655–2663. [Google Scholar] [CrossRef] [PubMed]
- Cozzolino, A.M.; Noce, V.; Battistelli, C.; Marchetti, A.; Grassi, G.; Cicchini, C.; Tripodi, M.; Amicone, L. Modulating the Substrate Stiffness to Manipulate Differentiation of Resident Liver Stem Cells and to Improve the Differentiation State of Hepatocytes. Stem Cells Int. 2016, 2016, 5481493. [Google Scholar] [CrossRef] [Green Version]
- Desai, S.S.; Tung, J.C.; Zhou, V.X.; Grenert, J.P.; Malato, Y.; Rezvani, M.; Espanol-Suner, R.; Willenbring, H.; Weaver, V.M.; Chang, T.T. Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha. Hepatology 2016, 64, 261–275. [Google Scholar] [CrossRef] [Green Version]
- Schrader, J.; Gordon-Walker, T.T.; Aucott, R.L.; van Deemter, M.; Quaas, A.; Walsh, S.; Benten, D.; Forbes, S.J.; Wells, R.G.; Iredale, J.P. Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology 2011, 53, 1192–1205. [Google Scholar] [CrossRef] [Green Version]
- Georges, P.C.; Hui, J.J.; Gombos, Z.; McCormick, M.E.; Wang, A.Y.; Uemura, M.; Mick, R.; Janmey, P.A.; Furth, E.E.; Wells, R.G. Increased stiffness of the rat liver precedes matrix deposition: Implications for fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 293, G1147–G1154. [Google Scholar] [CrossRef]
- Perepelyuk, M.; Terajima, M.; Wang, A.Y.; Georges, P.C.; Janmey, P.A.; Yamauchi, M.; Wells, R.G. Hepatic stellate cells and portal fibroblasts are the major cellular sources of collagens and lysyl oxidases in normal liver and early after injury. Am. J. Physiol. Gastrointest. Liver Physiol. 2013, 304, G605–G614. [Google Scholar] [CrossRef]
- Jones, M.G.; Andriotis, O.G.; Roberts, J.J.; Lunn, K.; Tear, V.J.; Cao, L.; Ask, K.; Smart, D.E.; Bonfanti, A.; Johnson, P.; et al. Nanoscale dysregulation of collagen structure-function disrupts mechano-homeostasis and mediates pulmonary fibrosis. Elife 2018, 7, e36354. [Google Scholar] [CrossRef]
- Perepelyuk, M.; Chin, L.; Cao, X.; van Oosten, A.; Shenoy, V.B.; Janmey, P.A.; Wells, R.G. Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics. PLoS ONE 2016, 11, e0146588. [Google Scholar] [CrossRef] [Green Version]
- Yin, M.; Glaser, K.J.; Talwalkar, J.A.; Chen, J.; Manduca, A.; Ehman, R.L. Hepatic MR Elastography: Clinical Performance in a Series of 1377 Consecutive Examinations. Radiology 2016, 278, 114–124. [Google Scholar] [CrossRef] [Green Version]
- Yin, M.; Talwalkar, J.A.; Glaser, K.J.; Manduca, A.; Grimm, R.C.; Rossman, P.J.; Fidler, J.L.; Ehman, R.L. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin. Gastroenterol. Hepatol. 2007, 5, 1207–1213. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Castera, L.; Friedrich-Rust, M.; Loomba, R. Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2019, 156, 1264–1281. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, J.; Venkatesh, S.K.; Yin, M. Advances in Magnetic Resonance Elastography of Liver. Magn. Reson. Imaging Clin. N. Am. 2020, 28, 331–340. [Google Scholar] [CrossRef] [PubMed]
- Dechene, A.; Sowa, J.P.; Gieseler, R.K.; Jochum, C.; Bechmann, L.P.; El Fouly, A.; Schlattjan, M.; Saner, F.; Baba, H.A.; Paul, A.; et al. Acute liver failure is associated with elevated liver stiffness and hepatic stellate cell activation. Hepatology 2010, 52, 1008–1016. [Google Scholar] [CrossRef] [PubMed]
- Arena, U.; Vizzutti, F.; Corti, G.; Ambu, S.; Stasi, C.; Bresci, S.; Moscarella, S.; Boddi, V.; Petrarca, A.; Laffi, G.; et al. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 2008, 47, 380–384. [Google Scholar] [CrossRef]
- Tapper, E.B.; Cohen, E.B.; Patel, K.; Bacon, B.; Gordon, S.; Lawitz, E.; Nelson, D.; Nasser, I.A.; Challies, T.; Afdhal, N. Levels of alanine aminotransferase confound use of transient elastography to diagnose fibrosis in patients with chronic hepatitis C virus infection. Clin. Gastroenterol. Hepatol. 2012, 10, 932–937. [Google Scholar] [CrossRef] [Green Version]
- Levental, I.; Levental, K.R.; Klein, E.A.; Assoian, R.; Miller, R.T.; Wells, R.G.; Janmey, P.A. A simple indentation device for measuring micrometer-scale tissue stiffness. J. Phys. Condens. Matter 2010, 22, 194120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, H.; Lin, F.; Huang, J.; Xiong, C. Anisotropic stiffness gradient-regulated mechanical guidance drives directional migration of cancer cells. Acta Biomater. 2020, 106, 181–192. [Google Scholar] [CrossRef] [PubMed]
- Balog, S.; Li, Y.; Ogawa, T.; Miki, T.; Saito, T.; French, S.W.; Asahina, K. Development of Capsular Fibrosis Beneath the Liver Surface in Humans and Mice. Hepatology 2020, 71, 291–305. [Google Scholar] [CrossRef] [PubMed]
- Nia, H.T.; Liu, H.; Seano, G.; Datta, M.; Jones, D.; Rahbari, N.; Incio, J.; Chauhan, V.P.; Jung, K.; Martin, J.D.; et al. Solid stress and elastic energy as measures of tumour mechanopathology. Nat. Biomed. Eng. 2016, 1, 3987. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Munn, L.L.; Nia, H.T. Mechanosensing tensile solid stresses. Proc. Natl. Acad. Sci. USA 2019, 116, 21960–21962. [Google Scholar] [CrossRef] [PubMed]
- Nieskoski, M.D.; Marra, K.; Gunn, J.R.; Kanick, S.C.; Doyley, M.M.; Hasan, T.; Pereira, S.P.; Stuart Trembly, B.; Pogue, B.W. Separation of Solid Stress From Interstitial Fluid Pressure in Pancreas Cancer Correlates With Collagen Area Fraction. J. Biomech. Eng. 2017, 139. [Google Scholar] [CrossRef]
- Seano, G.; Nia, H.T.; Emblem, K.E.; Datta, M.; Ren, J.; Krishnan, S.; Kloepper, J.; Pinho, M.C.; Ho, W.W.; Ghosh, M.; et al. Solid stress in brain tumours causes neuronal loss and neurological dysfunction and can be reversed by lithium. Nat. Biomed. Eng. 2019, 3, 230–245. [Google Scholar] [CrossRef]
- Nieskoski, M.D.; Marra, K.; Gunn, J.R.; Hoopes, P.J.; Doyley, M.M.; Hasan, T.; Trembly, B.S.; Pogue, B.W. Collagen Complexity Spatially Defines Microregions of Total Tissue Pressure in Pancreatic Cancer. Sci. Rep. 2017, 7, 10093. [Google Scholar] [CrossRef]
- DuFort, C.C.; DelGiorno, K.E.; Carlson, M.A.; Osgood, R.J.; Zhao, C.; Huang, Z.; Thompson, C.B.; Connor, R.J.; Thanos, C.D.; Brockenbrough, J.S.; et al. Interstitial Pressure in Pancreatic Ductal Adenocarcinoma Is Dominated by a Gel-Fluid Phase. Biophys. J. 2016, 110, 2106–2119. [Google Scholar] [CrossRef] [Green Version]
- Jacobetz, M.A.; Chan, D.S.; Neesse, A.; Bapiro, T.E.; Cook, N.; Frese, K.K.; Feig, C.; Nakagawa, T.; Caldwell, M.E.; Zecchini, H.I.; et al. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut 2013, 62, 112–120. [Google Scholar] [CrossRef]
- DuFort, C.C.; DelGiorno, K.E.; Hingorani, S.R. Mounting Pressure in the Microenvironment: Fluids, Solids, and Cells in Pancreatic Ductal Adenocarcinoma. Gastroenterology 2016, 150, 1545–1557. [Google Scholar] [CrossRef] [Green Version]
- Hosein, A.N.; Brekken, R.A.; Maitra, A. Pancreatic cancer stroma: An update on therapeutic targeting strategies. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 487–505. [Google Scholar] [CrossRef]
- Santha, P.; Lenggenhager, D.; Finstadsveen, A.; Dorg, L.; Tondel, K.; Amrutkar, M.; Gladhaug, I.P.; Verbeke, C. Morphological Heterogeneity in Pancreatic Cancer Reflects Structural and Functional Divergence. Cancers 2021, 13, 895. [Google Scholar] [CrossRef] [PubMed]
- Li, W.; Li, P.; Li, N.; Du, Y.; Lu, S.; Elad, D.; Long, M. Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model. Am. J. Physiol. Gastrointest. Liver Physiol. 2020. [Google Scholar] [CrossRef]
- Caliari, S.R.; Perepelyuk, M.; Cosgrove, B.D.; Tsai, S.J.; Lee, G.Y.; Mauck, R.L.; Wells, R.G.; Burdick, J.A. Stiffening hydrogels for investigating the dynamics of hepatic stellate cell mechanotransduction during myofibroblast activation. Sci. Rep. 2016, 6, 21387. [Google Scholar] [CrossRef] [Green Version]
- Olsen, A.L.; Bloomer, S.A.; Chan, E.P.; Gaca, M.D.; Georges, P.C.; Sackey, B.; Uemura, M.; Janmey, P.A.; Wells, R.G. Hepatic stellate cells require a stiff environment for myofibroblastic differentiation. Am. J. Physiol. Gastrointest. Liver Physiol. 2011, 301, G110–G118. [Google Scholar] [CrossRef] [Green Version]
- Li, Z.; Dranoff, J.A.; Chan, E.P.; Uemura, M.; Sevigny, J.; Wells, R.G. Transforming growth factor-beta and substrate stiffness regulate portal fibroblast activation in culture. Hepatology 2007, 46, 1246–1256. [Google Scholar] [CrossRef] [PubMed]
- Mederacke, I.; Hsu, C.C.; Troeger, J.S.; Huebener, P.; Mu, X.; Dapito, D.H.; Pradere, J.P.; Schwabe, R.F. Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology. Nat. Commun. 2013, 4, 2823. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Puche, J.E.; Lee, Y.A.; Jiao, J.; Aloman, C.; Fiel, M.I.; Munoz, U.; Kraus, T.; Lee, T.; Yee, H.F., Jr.; Friedman, S.L. A novel murine model to deplete hepatic stellate cells uncovers their role in amplifying liver damage in mice. Hepatology 2013, 57, 339–350. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baglieri, J.; Brenner, D.A.; Kisseleva, T. The Role of Fibrosis and Liver-Associated Fibroblasts in the Pathogenesis of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2019, 20, 1723. [Google Scholar] [CrossRef] [Green Version]
- Janku, F.; Kaseb, A.O.; Tsimberidou, A.M.; Wolff, R.A.; Kurzrock, R. Identification of novel therapeutic targets in the PI3K/AKT/mTOR pathway in hepatocellular carcinoma using targeted next generation sequencing. Oncotarget 2014, 5, 3012–3022. [Google Scholar] [CrossRef] [Green Version]
- Zhao, G.; Cui, J.; Qin, Q.; Zhang, J.; Liu, L.; Deng, S.; Wu, C.; Yang, M.; Li, S.; Wang, C. Mechanical stiffness of liver tissues in relation to integrin beta1 expression may influence the development of hepatic cirrhosis and hepatocellular carcinoma. J. Surg. Oncol. 2010, 102, 482–489. [Google Scholar] [CrossRef]
- Gao, X.; Qiao, X.; Xing, X.; Huang, J.; Qian, J.; Wang, Y.; Zhang, Y.; Zhang, X.; Li, M.; Cui, J.; et al. Matrix Stiffness-Upregulated MicroRNA-17-5p Attenuates the Intervention Effects of Metformin on HCC Invasion and Metastasis by Targeting the PTEN/PI3K/Akt Pathway. Front. Oncol. 2020, 10, 1563. [Google Scholar] [CrossRef]
- Li, L.; Zhao, G.D.; Shi, Z.; Qi, L.L.; Zhou, L.Y.; Fu, Z.X. The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol. Lett. 2016, 12, 3045–3050. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, L.; Shi, Y.; Jiang, C.Y.; Wei, L.X.; Wang, Y.L.; Dai, G.H. Expression and prognostic role of pan-Ras, Raf-1, pMEK1 and pERK1/2 in patients with hepatocellular carcinoma. Eur. J. Surg. Oncol. 2011, 37, 513–520. [Google Scholar] [CrossRef] [PubMed]
- Chung, S.I.; Moon, H.; Ju, H.L.; Kim, D.Y.; Cho, K.J.; Ribback, S.; Dombrowski, F.; Calvisi, D.F.; Ro, S.W. Comparison of liver oncogenic potential among human RAS isoforms. Oncotarget 2016, 7, 7354–7366. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yuan, W.C.; Pepe-Mooney, B.; Galli, G.G.; Dill, M.T.; Huang, H.T.; Hao, M.; Wang, Y.; Liang, H.; Calogero, R.A.; Camargo, F.D. NUAK2 is a critical YAP target in liver cancer. Nat. Commun. 2018, 9, 4834. [Google Scholar] [CrossRef] [Green Version]
- Bisso, A.; Filipuzzi, M.; Gamarra Figueroa, G.P.; Brumana, G.; Biagioni, F.; Doni, M.; Ceccotti, G.; Tanaskovic, N.; Morelli, M.J.; Pendino, V.; et al. Cooperation Between MYC and beta-Catenin in Liver Tumorigenesis Requires Yap/Taz. Hepatology 2020, 72, 1430–1443. [Google Scholar] [CrossRef] [PubMed]
- Wu, L.; Zhang, Q.; Mo, W.; Feng, J.; Li, S.; Li, J.; Liu, T.; Xu, S.; Wang, W.; Lu, X.; et al. Quercetin prevents hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing autophagy via the TGF-beta1/Smads and PI3K/Akt pathways. Sci. Rep. 2017, 7, 9289. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Su, J.; Morgani, S.M.; David, C.J.; Wang, Q.; Er, E.E.; Huang, Y.H.; Basnet, H.; Zou, Y.; Shu, W.; Soni, R.K.; et al. TGF-beta orchestrates fibrogenic and developmental EMTs via the RAS effector RREB1. Nature 2020, 577, 566–571. [Google Scholar] [CrossRef]
- Liu, F.; Lagares, D.; Choi, K.M.; Stopfer, L.; Marinkovic, A.; Vrbanac, V.; Probst, C.K.; Hiemer, S.E.; Sisson, T.H.; Horowitz, J.C.; et al. Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis. Am. J. Physiol. Lung. Cell Mol. Physiol. 2015, 308, L344–L357. [Google Scholar] [CrossRef] [Green Version]
- Du, K.; Hyun, J.; Premont, R.T.; Choi, S.S.; Michelotti, G.A.; Swiderska-Syn, M.; Dalton, G.D.; Thelen, E.; Rizi, B.S.; Jung, Y.; et al. Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells. Gastroenterology 2018, 154, 1465–1479. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Francalanci, P.; Giovannoni, I.; De Stefanis, C.; Romito, I.; Grimaldi, C.; Castellano, A.; D’Oria, V.; Alaggio, R.; Alisi, A. Focal Adhesion Kinase (FAK) Over-Expression and Prognostic Implication in Pediatric Hepatocellular Carcinoma. Int. J. Mol. Sci. 2020, 21, 5795. [Google Scholar] [CrossRef] [PubMed]
- Zhao, X.K.; Yu, L.; Cheng, M.L.; Che, P.; Lu, Y.Y.; Zhang, Q.; Mu, M.; Li, H.; Zhu, L.L.; Zhu, J.J.; et al. Focal Adhesion Kinase Regulates Hepatic Stellate Cell Activation and Liver Fibrosis. Sci. Rep. 2017, 7, 4032. [Google Scholar] [CrossRef]
- Gnani, D.; Romito, I.; Artuso, S.; Chierici, M.; De Stefanis, C.; Panera, N.; Crudele, A.; Ceccarelli, S.; Carcarino, E.; D’Oria, V.; et al. Focal adhesion kinase depletion reduces human hepatocellular carcinoma growth by repressing enhancer of zeste homolog 2. Cell Death Differ. 2017, 24, 889–902. [Google Scholar] [CrossRef] [PubMed]
- Nava, M.M.; Miroshnikova, Y.A.; Biggs, L.C.; Whitefield, D.B.; Metge, F.; Boucas, J.; Vihinen, H.; Jokitalo, E.; Li, X.; Garcia Arcos, J.M.; et al. Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage. Cell 2020, 181, 800–817. [Google Scholar] [CrossRef] [PubMed]
- Elosegui-Artola, A.; Andreu, I.; Beedle, A.E.M.; Lezamiz, A.; Uroz, M.; Kosmalska, A.J.; Oria, R.; Kechagia, J.Z.; Rico-Lastres, P.; Le Roux, A.L.; et al. Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores. Cell 2017, 171, 1397–1410. [Google Scholar] [CrossRef]
- Hatch, E.M.; Hetzer, M.W. Nuclear envelope rupture is induced by actin-based nucleus confinement. J. Cell Biol. 2016, 215, 27–36. [Google Scholar] [CrossRef] [Green Version]
- Koushki, N.; Ghagre, A.; Srivastava, L.K.; Sitaras, C.; Yoshie, H.; Molter, C.; Ehrlicher, A.J. Lamin A redistribution mediated by nuclear deformation determines dynamic localization of YAP. bioRxiv 2020. [Google Scholar] [CrossRef] [Green Version]
- Guixe-Muntet, S.; Ortega-Ribera, M.; Wang, C.; Selicean, S.; Andreu, I.; Kechagia, J.Z.; Fondevila, C.; Roca-Cusachs, P.; Dufour, J.F.; Bosch, J.; et al. Nuclear deformation mediates liver cell mechanosensing in cirrhosis. JHEP Rep. 2020, 2, 100145. [Google Scholar] [CrossRef]
- Cattin, C.J.; Duggelin, M.; Martinez-Martin, D.; Gerber, C.; Muller, D.J.; Stewart, M.P. Mechanical control of mitotic progression in single animal cells. Proc. Natl. Acad. Sci. USA 2015, 112, 11258–11263. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tse, J.M.; Cheng, G.; Tyrrell, J.A.; Wilcox-Adelman, S.A.; Boucher, Y.; Jain, R.K.; Munn, L.L. Mechanical compression drives cancer cells toward invasive phenotype. Proc. Natl. Acad. Sci. USA 2012, 109, 911–916. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tse, H.T.; Weaver, W.M.; Di Carlo, D. Increased asymmetric and multi-daughter cell division in mechanically confined microenvironments. PLoS ONE 2012, 7, e38986. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Desmaison, A.; Guillaume, L.; Triclin, S.; Weiss, P.; Ducommun, B.; Lobjois, V. Impact of physical confinement on nuclei geometry and cell division dynamics in 3D spheroids. Sci. Rep. 2018, 8, 8785. [Google Scholar] [CrossRef] [Green Version]
- Noatynska, A.; Gotta, M.; Meraldi, P. Mitotic spindle (DIS)orientation and DISease: Cause or consequence? J. Cell Biol. 2012, 199, 1025–1035. [Google Scholar] [CrossRef] [Green Version]
- Lancaster, O.M.; Le Berre, M.; Dimitracopoulos, A.; Bonazzi, D.; Zlotek-Zlotkiewicz, E.; Picone, R.; Duke, T.; Piel, M.; Baum, B. Mitotic rounding alters cell geometry to ensure efficient bipolar spindle formation. Dev. Cell 2013, 25, 270–283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taubenberger, A.V.; Baum, B.; Matthews, H.K. The Mechanics of Mitotic Cell Rounding. Front. Cell Dev. Biol. 2020, 8, 687. [Google Scholar] [CrossRef] [PubMed]
- Knouse, K.A.; Lopez, K.E.; Bachofner, M.; Amon, A. Chromosome Segregation Fidelity in Epithelia Requires Tissue Architecture. Cell 2018, 175, 200–211. [Google Scholar] [CrossRef] [Green Version]
- Knouse, K.A.; Davoli, T.; Elledge, S.J.; Amon, A. Aneuploidy in Cancer: Seq-ing Answers to Old Questions. Annu. Rev. Cancer Biol. 2017, 1, 335–354. [Google Scholar] [CrossRef]
- Irianto, J.; Xia, Y.; Pfeifer, C.R.; Athirasala, A.; Ji, J.; Alvey, C.; Tewari, M.; Bennett, R.R.; Harding, S.M.; Liu, A.J.; et al. DNA Damage Follows Repair Factor Depletion and Portends Genome Variation in Cancer Cells after Pore Migration. Curr. Biol. 2017, 27, 210–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pfeifer, C.R.; Xia, Y.; Zhu, K.; Liu, D.; Irianto, J.; Garcia, V.M.M.; Millan, L.M.S.; Niese, B.; Harding, S.; Deviri, D.; et al. Constricted migration increases DNA damage and independently represses cell cycle. Mol. Biol. Cell 2018, 29, 1948–1962. [Google Scholar] [CrossRef]
- Xia, Y.; Ivanovska, I.L.; Zhu, K.; Smith, L.; Irianto, J.; Pfeifer, C.R.; Alvey, C.M.; Ji, J.; Liu, D.; Cho, S.; et al. Nuclear rupture at sites of high curvature compromises retention of DNA repair factors. J. Cell Biol. 2018, 217, 3796–3808. [Google Scholar] [CrossRef] [PubMed]
- Shah, P.; Hobson, C.M.; Cheng, S.; Colville, M.J.; Paszek, M.J.; Superfine, R.; Lammerding, J. Nuclear Deformation Causes DNA Damage by Increasing Replication Stress. Curr. Biol. 2021, 31, 753–765. [Google Scholar] [CrossRef]
- Chin, L.; Theise, N.D.; Loneker, A.E.; Janmey, P.A.; Wells, R.G. Lipid droplets disrupt mechanosensing in human hepatocytes. Am. J. Physiol. Gastrointest. Liver Physiol. 2020, 319, G11–G22. [Google Scholar] [CrossRef]
- Heo, S.J.; Han, W.M.; Szczesny, S.E.; Cosgrove, B.D.; Elliott, D.M.; Lee, D.A.; Duncan, R.L.; Mauck, R.L. Mechanically Induced Chromatin Condensation Requires Cellular Contractility in Mesenchymal Stem Cells. Biophys. J. 2016, 111, 864–874. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brunner, S.F.; Roberts, N.D.; Wylie, L.A.; Moore, L.; Aitken, S.J.; Davies, S.E.; Sanders, M.A.; Ellis, P.; Alder, C.; Hooks, Y.; et al. Somatic mutations and clonal dynamics in healthy and cirrhotic human liver. Nature 2019, 574, 538–542. [Google Scholar] [CrossRef]
- Pfeifer, C.R.; Alvey, C.M.; Irianto, J.; Discher, D.E. Genome variation across cancers scales with tissue stiffness—An invasion-mutation mechanism and implications for immune cell infiltration. Curr. Opin. Syst. Biol. 2017, 2, 103–114. [Google Scholar] [CrossRef] [Green Version]
- Kanwal, F.; Kramer, J.R.; Mapakshi, S.; Natarajan, Y.; Chayanupatkul, M.; Richardson, P.A.; Li, L.; Desiderio, R.; Thrift, A.P.; Asch, S.M.; et al. Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease. Gastroenterology 2018, 155, 1828–1837. [Google Scholar] [CrossRef] [Green Version]
- Sanyal, A.; Poklepovic, A.; Moyneur, E.; Barghout, V. Population-based risk factors and resource utilization for HCC: US perspective. Curr. Med. Res. Opin. 2010, 26, 2183–2191. [Google Scholar] [CrossRef]
- Welzel, T.M.; Graubard, B.I.; Zeuzem, S.; El-Serag, H.B.; Davila, J.A.; McGlynn, K.A. Metabolic syndrome increases the risk of primary liver cancer in the United States: A study in the SEER-Medicare database. Hepatology 2011, 54, 463–471. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Loneker, A.E.; Wells, R.G. Perspective: The Mechanobiology of Hepatocellular Carcinoma. Cancers 2021, 13, 4275. https://doi.org/10.3390/cancers13174275
Loneker AE, Wells RG. Perspective: The Mechanobiology of Hepatocellular Carcinoma. Cancers. 2021; 13(17):4275. https://doi.org/10.3390/cancers13174275
Chicago/Turabian StyleLoneker, Abigail E., and Rebecca G. Wells. 2021. "Perspective: The Mechanobiology of Hepatocellular Carcinoma" Cancers 13, no. 17: 4275. https://doi.org/10.3390/cancers13174275