Mechanobiology of cancerogenesis
Authors:
Martina Raudenská 1; Jiří Navrátil 2; MUDr. Jaromír Gumulec 2; Michal Masařík 1-3
Authors place of work:
Fyziologický ústav, LF MU Brno
1; Ústav patologické fyziologie, LF MU Brno
2; BIOCEV – Biotechnologické a biomedicínské centrum AV ČR, PF UK a 1. LF UK, Vestec
3
Published in the journal:
Klin Onkol 2021; 34(3): 202-210
Category:
Review
doi:
https://doi.org/10.48095/ccko2021202
Summary
Background: Within the tumour microenvironment, tumour cells are exposed to different mechanical stimuli such as compression stress, cell-cell and cell-extracellular matrix traction forces, interstitial fluid pressure, and shear stress. Cells actively sense and process this information by the mechanism of mechanotransduction to make decisions about their growth, motility, and differentiation. Indeed, the mechanical properties of the tumour microenvironment can deeply influence the behaviour of cancer cells and promote cancerogenesis. During tumour progression, desmoplasia arises and a positive feedback loop between the stiffening extracellular matrix and the properties enabling tumour expansion is established. Tumour cells can use mechanic stimuli to promote proliferation, increase their migratory and invasive potential, and induce therapeutic resistance. Mechanobiology is a progressive multidisciplinary field which studies how mechanical forces influence the behaviour of cells or tissues and may provide some interesting targets for cancer therapy. Purpose: In this review, we discuss the mechanical properties of cancer cells and describe the tumour promoting effect of the transformed extracellular matrix. We propose that the differences in the mechanobiology of cells and extracellular matrix are significant enough to facilitate tumorigenesis and may provide interesting targets for cancer therapy.
Keywords:
mechanobiology – cancer – extracellular matrix – mechanotransduction – shear stress – therapy resistence
Zdroje
- Jansen KA, Donato DM, Balcioglu HE et al. A guide to mechanobiology: where biology and physics meet. Biochim Biophys Acta 2015; 1853(11, Pt B): 3043–3052. doi: doi: 10.1016/ j.bbamcr.2015.05.007.
- Northcott JM, Dean IS, Mouw JK et al. Feeling stress: the mechanics of cancer progression and aggression. Front Cell Dev Biol 2018; 6: 17. doi: 10.3389/ fcell.2018.00017.
- Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol 2012; 196(4): 395–406. doi: 10.1083/ jcb.201102147.
- Morgan JE, Gross JG, Pagel CN et al. Myogenic cell proliferation and generation of a reversible tumorigenic phenotype are triggered by preirradiation of the recipient site. J Cell Biol 2002; 157(4): 693–702. doi: 10.1083/ jcb.200108047.
- Gieni RS, Hendzel MJ. Mechanotransduction from the ECM to the genome: are the pieces now in place? J Cell Biochem 2008; 104(6): 1964–1987. doi: 10.1002/ jcb.21364.
- Bissell MJ, Kenny PA, Radisky DC. Microenvironmental regulators of tissue structure and function also regulate tumor induction and progression: the role of extracellular matrix and its degrading enzymes. Cold Spring Harb Symp Quant Biol 2005; 70: 343–356. doi: 10.1101/ sqb.2005.70.013.
- Allard D, Stoker M, Gherardi E. A G2/ M cell cycle block in transformed cells by contact with normal neighbors. Cell Cycle 2003; 2(5): 484–487.
- Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol 2014; 15(12): 786–801. doi: 10.1038/ nrm3904.
- Theocharis AD, Skandalis SS, Gialeli C et al. Extracellular matrix structure. Adv Drug Deliv Rev 2016; 97: 4–27. doi: 10.1016/ j.addr.2015.11.001.
- Levental KR, Yu H, Kass L et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 2009; 139(5): 891–906. doi: 10.1016/ j.cell.2009.10. 027.
- Acerbi I, Cassereau L, Dean I et al. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr Biol (Camb) 2015; 7(10): 1120–1134. doi: 10.1039/ c5ib00040h.
- Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther 2007; 6(4): 1186–1197. doi: 10.1158/ 1535-7163.mct-06-0686.
- Tuxhorn JA, Ayala GE, Smith MJ et al. Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. Clin Cancer Res 2002; 8(9): 2912–2923.
- Miller BW, Morton JP, Pinese M et al. Targeting the LOX/ hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy. EMBO Mol Med 2015; 7(8): 1063–1076. doi: 10.15252/ emmm.201404827.
- Pickup MW, Laklai H, Acerbi I et al. Stromally derived lysyl oxidase promotes metastasis of transforming growth factor-b-deficient mouse mammary carcinomas. Cancer Res 2013; 73(17): 5336–5346. doi: 10.1158/ 0008-5472.can-13-0012.
- Svitkina TM. Filopodia and Lamellipodia. [online]. Available from: https:/ / www.researchgate.net/ publication/ 301856217_Filopodia_and_Lamellipodia.
- Alblazi KM, Siar CH. Cellular protrusions--lamellipodia, filopodia, invadopodia and podosomes--and their roles in progression of orofacial tumours: current understanding. Asian Pac J Cancer Prev 2015; 16(6): 2187–2191. doi: 10.7314/ apjcp.2015.16.6.2187.
- Collin O, Tracqui P, Stephanou A et al. Spatiotemporal dynamics of actin-rich adhesion microdomains: influence of substrate flexibility. J Cell Sci 2006; 119 (Pt 9): 1914–1925. doi: 10.1242/ jcs.02838.
- Wong S, Guo WH, Wang YL. Fibroblasts probe substrate rigidity with filopodia extensions before occupying an area. Proc Natl Acad Sci USA 2014; 111(48): 17176–17181. doi: 10.1073/ pnas.1412285111.
- Fraley SI, Wu PH, He L et al. Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP utility by spatially and temporally directing protrusions. Sci Rep 2015; 5: 14580. doi: 10.1038/ srep14580.
- Han W, Chen S, Yuan W et al. Oriented collagen fibers direct tumor cell intravasation. Proc Natl Acad Sci USA 2016; 113(40): 11208–11213. doi: 10.1073/ pnas.1610347113.
- Lopez JI, Kang I, You WK et al. In situ force mapping of mammary gland transformation. Integr Biol (Camb) 2011; 3(9): 910–921. doi: 10.1039/ c1ib00043h.
- Provenzano PP, Eliceiri KW, Campbell JM et al. Collagen reorganization at the tumor-stromal interface facilitates local invasion. BMC Med 2006; 4(1): 38. doi: 10.1186/ 1741-7015-4-38.
- Stella GM, Kolling S, Benvenuti S et al. Lung-seeking metastases. Cancers (Basel) 2019; 11(7): 1010. doi: 10.3390/ cancers11071010.
- Centeno BA. Pathology of liver metastases. Cancer Control 2006; 13(1): 13–26. doi: 10.1177/ 107327480601300103.
- Zeisberg M, Kalluri R. Cellular mechanisms of tissue fibrosis. 1. Common and organ-specific mechanisms associated with tissue fibrosis. Am J Physiol Cell Physiol 2013; 304(3): C216–C225. doi: 10.1152/ ajpcell.00328.2012.
- Wang N, Butler J, Ingber D. Mechanotransduction across the cell surface and through the cytoskeleton. Science 1993; 260(5111): 1124–1127. doi: 10.1126/ science.7684161.
- Mitra SK, Schlaepfer DD. Integrin-regulated FAK-Src signaling in normal and cancer cells. Curr Opin Cell Biol 2006; 18(5): 516–523. doi: 10.1016/ j.ceb.2006.08.011.
- Price LS, Leng J, Schwartz MA et al. Activation of Rac and Cdc42 by integrins mediates cell spreading. Mol Biol Cell 1998; 9(7): 1863–1871. doi: 10.1091/ mbc.9.7.1863.
- Steffen A, Ladwein M, Dimchev GA et al. Rac function is crucial for cell migration but is not required for spreading and focal adhesion formation. J Cell Sci 2013; 126 (Pt 20): 4572–4588. doi: 10.1242/ jcs.118232.
- Nobes CD, Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 1995; 81(1): 53–62. doi: 10.1016/ 0092-8674(95)90370-4.
- He K, Sakai T, Tsukasaki Y et al. Myosin X is recruited to nascent focal adhesions at the leading edge and induces multi-cycle filopodial elongation. Sci Rep 2017; 7(1): 13685. doi: 10.1038/ s41598-017-06147-6.
- Berg JS, Cheney RE. Myosin-X is an unconventional myosin that undergoes intrafilopodial motility. Nat Cell Biol 2002; 4(3): 246–250. doi: 10.1038/ ncb762.
- Makowska KA, Hughes RE, White KJ et al. Specific myosins control actin organization, cell morphology, and migration in prostate cancer cells. Cell Rep 2015; 13(10): 2118–2125. doi: 10.1016/ j.celrep.2015.11.012.
- DeMali KA, Barlow CA, Burridge K. Recruitment of the Arp2/ 3 complex to vinculin : coupling membrane protrusion to matrix adhesion. J Cell Biol 2002; 159(5): 881–891. doi: 10.1083/ jcb.200206043.
- Paterno J, Vial IN, Wong VW et al. Akt-mediated mechanotransduction in murine fibroblasts during hypertrophic scar formation. Wound Repair Regen 2011; 19(1): 49–58. doi: 10.1111/ j.1524-475X.2010.00643.x.
- Xue Z, Zhang W, Desai LP et al. Increased mechanical strain imposed on murine lungs during ventilation in vivo depresses airway responsiveness and activation of protein kinase Akt. J Appl Physiol (1985) 2013; 114(11): 1506–1510. doi: 10.1152/ japplphysiol.01460.2012.
- Rubashkin MG, Cassereau L, Bainer R et al. Force engages vinculin and promotes tumor progression by enhancing PI3K activation of phosphatidylinositol (3,4,5)-triphosphate. Cancer Res 2014; 74(17): 4597–4611. doi: 10.1158/ 0008-5472.can-13-3698.
- Arthur WT, Petch LA, Burridge K. Integrin engagement suppresses RhoA activity via a c-Src-dependent mechanism. Curr Biol 2000; 10(12): 719–722. doi: 10.1016/ s0960-9822(00)00537-6.
- Huveneers S, Danen EH. Adhesion signaling – crosstalk between integrins, Src and Rho. J Cell Sci 2009; 122(8): 1059–1069. doi: 10.1242/ jcs.039446.
- Huynh J, Bordeleau F, Kraning-Rush CM et al. Substrate stiffness regulates PDGF-induced circular dorsal ruffle formation through MLCK. Cell Mol Bioeng 2013; 6(2): 10.1007/ s12195-013-0278-7. doi: 10.1007/ s12195-013-0278-7.
- Azimifar SB, Böttcher RT, Zanivan S et al. Induction of membrane circular dorsal ruffles requires co-signalling of integrin-ILK-complex and EGF receptor. J Cell Sci 2012; 125 (Pt 2): 435–448. doi: 10.1242/ jcs.091652.
- Li X, Zhou Y, Li Y et al. Autophagy: a novel mechanism of chemoresistance in cancers. Biomed Pharmacother 2019; 119: 109415. doi: 10.1016/ j.biopha.2019.109415.
- Balvan J, Gumulec J, Raudenska M et al. Oxidative stress resistance in metastatic prostate cancer: renewal by self-eating. PLoS One 2015; 10(12): e0145016. doi: 10.1371/ journal.pone.0145016.
- Totaro A, Zhuang Q, Panciera T et al. Cell phenotypic plasticity requires autophagic flux driven by YAP/ TAZ mechanotransduction. Proc Natl Acad Sci USA 2019; 116(36): 17848–17857. doi: 10.1073/ pnas.1908228 116.
- Jiang N, Dai Q, Su X et al. Role of PI3K/ AKT pathway in cancer: the framework of malignant behavior. Mol Biol Rep 2020; 47(6): 4587–4629. doi: 10.1007/ s11033-020-05435-1.
- Windham TC, Parikh NU, Siwak DR et al. Src activation regulates anoikis in human colon tumor cell lines. Oncogene 2002; 21(51): 7797–7807. doi: 10.1038/ sj.onc.1205989.
- Yoshida R, Sasaki T, Minami Y et al. Activation of Src signaling mediates acquired resistance to ALK inhibition in lung cancer. Int J Oncol 2017; 51(5): 1533–1540. doi: 10.3892/ ijo.2017.4140.
- Nguyen TV, Sleiman M, Moriarty T et al. Sorafenib resistance and JNK signaling in carcinoma during extracellular matrix stiffening. Biomaterials 2014; 35(22): 5749–5759. doi: 10.1016/ j.biomaterials.2014.03.058.
- Rice AJ, Cortes E, Lachowski D et al. Matrix stiffness induces epithelial-mesenchymal transition and promotes chemoresistance in pancreatic cancer cells. Oncogenesis 2017; 6(7): e352. doi: 10.1038/ oncsis.2017.54.
- Schrader J, Gordon-Walker TT, Aucott RL et al. Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology 2011; 53(4): 1192–1205. doi: 10.1002/ hep.24108.
- Liu C, Liu Y, Xie HG et al. Role of three-dimensional matrix stiffness in regulating the chemoresistance of hepatocellular carcinoma cells. Biotechnol Appl Biochem 2015; 62(4): 556–562. doi: 10.1002/ bab.1302.
- You Y, Zheng Q, Dong Y et al. Matrix stiffness-mediated effects on stemness characteristics occurring in HCC cells. Oncotarget 2016; 7(22): 32221–32231. doi: 10.18632/ oncotarget.8515.
- Joyce MH, Lu C, James ER et al. Phenotypic basis for matrix stiffness-dependent chemoresistance of breast cancer cells to doxorubicin. Front Oncol 2018; 8: 337. doi: 10.3389/ fonc.2018.00337.
- Orafaie A, Matin MM, Sadeghian H. The importance of 15-lipoxygenase inhibitors in cancer treatment. Cancer Metastasis Rev 2018; 37(2): 397–408. doi: 10.1007/ s10555-018-9738-9.
- Saatci O, Kaymak A, Raza U et al. Targeting lysyl oxidase (LOX) overcomes chemotherapy resistance in triple negative breast cancer. Nat Commun 2020; 11(1): 2416. doi: 10.1038/ s41467-020-16199-4.
- Cox TR, Rumney RM, Schoof EM et al. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature 2015; 522(7554): 106–110. doi: 10.1038/ nature14492.
- Min C, Kirsch KH, Zhao Y et al. The tumor suppressor activity of the lysyl oxidase propeptide reverses the invasive phenotype of Her-2/ neu-driven breast cancer. Cancer Res 2007; 67(3): 1105–1112. doi: 10.1158/ 0008-5472.can-06-3867.
- Eke I, Deuse Y, Hehlgans S et al. b₁Integrin/ FAK/ cortactin signaling is essential for human head and neck cancer resistance to radiotherapy. J Clin Invest 2012; 122(4): 1529–1540. doi: 10.1172/ jci61350.
- Golubovskaya VM. Targeting FAK in human cancer: from finding to first clinical trials. Front Biosci (Landmark Ed) 2014; 19: 687–706. doi: 10.2741/ 4236.
- Heffler M, Golubovskaya VM, Dunn KM et al. Focal adhesion kinase autophosphorylation inhibition decreases colon cancer cell growth and enhances the efficacy of chemotherapy. Cancer Biol Ther 2013; 14(8): 761–772. doi: 10.4161/ cbt.25185.
- Hochwald SN, Nyberg C, Zheng M et al. A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer. Cell Cycle 2009; 8(15): 2435–2443. doi: 10.4161/ cc.8.15.9145.
- Gerber DE, Camidge DR, Morgensztern D et al. Phase 2 study of the focal adhesion kinase inhibitor defactinib (VS-6063) in previously treated advanced KRAS mutant non-small cell lung cancer. Lung Cancer 2020; 139: 60–67. doi: 10.1016/ j.lungcan.2019.10.033.
- Mohanty A, Pharaon RR, Nam A et al. FAK-targeted and combination therapies for the treatment of cancer: an overview of phase I and II clinical trials. Expert Opin Investig Drugs 2020; 29(4): 399–409. doi: 10.1080/ 13543784.2020.1740680.
- Kurenova EV, Hunt DL, He D et al. Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo. J Med Chem 2009; 52(15): 4716–4724. doi: 10.1021/ jm900159g.
- Alday-Parejo B, Stupp R, Rüegg C. Are integrins still practicable targets for anti-cancer therapy? Cancers 2019; 11(7): 978. doi: 10.3390/ cancers11070978.
- Klapproth E, Dickreuter E, Zakrzewski F et al. Whole exome sequencing identifies mTOR and KEAP1 as potential targets for radiosensitization of HNSCC cells refractory to EGFR and b1 integrin inhibition. Oncotarget 2018; 9(26): 18099–18114. doi: 10.18632/ oncotarget.24266.
- Huang SW, Chyuan IT, Shiue C et al. Lovastatin-mediated MCF-7 cancer cell death involves LKB1-AMPK-p38MAPK-p53-survivin signalling cascade. J Cell Mol Med 2020; 24(2): 1822–1836. doi: 10.1111/ jcmm.14879.
- Kidera Y, Tsubaki M, Yamazoe Y et al. Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/ Rho-associated coiled-coil-containing protein kinase pathway. J Exp Clin Cancer Res 2010; 29(1): 127. doi: 10.1186/ 1756-9966-29-127.
- Wang Z, Zhang L, Wan Z et al. Atorvastatin and caffeine in combination regulates apoptosis, migration, invasion and tumorspheres of prostate cancer cells. Pathol Oncol Res 2020; 26(1): 209–216. doi: 10.1007/ s12253-018-0415-7.
- Sorrentino G, Ruggeri N, Specchia V et al. Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol 2014; 16(4): 357–366. doi: 10.1038/ ncb2936.
- Huang Q, Hu X, He W et al. Fluid shear stress and tumor metastasis. Am J Cancer Res 2018; 8(5): 763–777.
- Mitchell M, King M. Computational and experimental models of cancer cell response to fluid shear stress. Front Oncol 2013; 3: 44: doi: 10.3389/ fonc.2013.00044.
- Wirtz D, Konstantopoulos K, Searson PC. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer 2011; 11(7): 512–522. doi: 10.1038/ nrc3080.
- Fan R, Emery T, Zhang Y et al. Circulatory shear flow alters the viability and proliferation of circulating colon cancer cells. Sci Rep 2016; 6: 27073. doi: 10.1038/ srep27073.
- Davies PF, Spaan JA, Krams R. Shear stress biology of the endothelium. Ann Biomed Eng 2005; 33(12): 1714–1718. doi: 10.1007/ s10439-005-8774-0.
- von Sengbusch A, Gassmann P, Fisch KM et al. Focal adhesion kinase regulates metastatic adhesion of carcinoma cells within liver sinusoids. Am J Pathol 2005; 166(2): 585–596. doi: 10.1016/ s0002-9440(10)62280-8.
- Regmi S, Fu A, Luo KQ. High shear stresses under exercise condition destroy circulating tumor cells in a microfluidic system. Sci Rep 2017; 7(1): 39975. doi: 10.1038/ srep39975.
- Thompson BJ. YAP/ TAZ: drivers of tumor growth, metastasis, and resistance to therapy. BioEssays 2020; 42(5): 1900162. doi: 10.1002/ bies.201900162.
- Lee HJ, Diaz MF, Price KM et al. Fluid shear stress activates YAP1 to promote cancer cell motility. Nat Commun 2017; 8: 14122. doi: 10.1038/ ncomms14122.
- Guck J, Schinkinger S, Lincoln B et al. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys J 2005; 88(5): 3689–3698. doi: 10.1529/ biophysj.104.045476.
- Rao KM, Cohen HJ. Actin cytoskeletal network in aging and cancer. Mutat Res 1991; 256(2–6):139–148. doi: 10.1016/ 0921-8734(91)90007-x.
- Alibert C, Goud B, Manneville JB. Are cancer cells really softer than normal cells? Biol Cell 2017; 109(5): 167–189. doi: 10.1111/ boc.201600078.
- Paul CD, Mistriotis P, Konstantopoulos K. Cancer cell motility: lessons from migration in confined spaces. Nat Rev Cancer 2017; 17(2): 131–140. doi: 10.1038/ nrc.2016.123.
- Sun Q, Luo T, Ren Y et al. Competition between human cells by entosis. Cell Res 2014; 24(11): 1299–1310. doi: 10.1038/ cr.2014.138.
- Islam M, Mezencev R, McFarland B et al. Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy. Cell Death Dis 2018; 9(2): 239. doi: 10.1038/ s41419-018-0266-x.
- Lautscham Lena A, Kämmerer C, Lange Janina R et al. Migration in confined 3D environments is determined by a combination of adhesiveness, nuclear volume, contractility, and cell stiffness. Biophys J 2015; 109(5): 900–913. doi: 10.1016/ j.bpj.2015.07.025.
- Schoumacher M, Goldman R D, Louvard D et al. Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia. J Cell Biol 2010; 189(3): 541–556. doi: 10.1083/ jcb.200909113.
- Wolf K, Te Lindert M, Krause M et al. Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J Cell Biol 2013; 201(7): 1069–1084. doi: 10.1083/ jcb.201210152.
- Denais C, Lammerding J. Nuclear mechanics in cancer. Adv Exp Med Biol 2014; 773: 435–470. doi: 10.1007/ 978-1-4899-8032-8_20.
- Zink D, Fischer AH, Nickerson JA. Nuclear structure in cancer cells. Nat Rev Cancer 2004; 4(9): 677–687. doi: 10.1038/ nrc1430.
- Rowat AC, Jaalouk DE, Zwerger M et al. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. J Biol Chem. 2013; 288(12): 8610–8618. doi: 10.1074/ jbc.M112.441535.
- Burke B. When cells push the envelope. Science 2016; 352(6283): 295–296. doi: 10.1126/ science.aaf7 735.
- Mitchell MJ, Denais C, Chan MF et al. Lamin A/ C deficiency reduces circulating tumor cell resistance to fluid shear stress. Am J Physiol Cell Physiol 2015; 309(11): C736–C746. doi: 10.1152/ ajpcell.00050.2015.
- Kong L, Schäfer G, Bu H et al. Lamin A/ C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/ AKT/ PTEN pathway. Carcinogenesis 2012; 33(4): 751–759. doi: 10.1093/ carcin/ bg s022.
- Park S, Kim YS, Kim DY et al. PI3K pathway in prostate cancer: all resistant roads lead to PI3K. Biochim Biophys Acta Rev Cancer 2018; 1870(2): 198–206. doi: 10.1016/ j.bbcan.2018.09.001.
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