Deciphering Biophysical Modulation in Ovarian Cancer Cells.
CSK Tyrosine-Protein Kinase
/ antagonists & inhibitors
Cell Adhesion
/ physiology
Cell Line, Tumor
Cell Proliferation
/ drug effects
Down-Regulation
/ drug effects
Female
Focal Adhesion Kinase 1
/ antagonists & inhibitors
Humans
MAP Kinase Kinase Kinases
/ metabolism
Mechanotransduction, Cellular
Ovarian Neoplasms
/ metabolism
Protein Kinase Inhibitors
/ pharmacology
Signal Transduction
/ physiology
Tumor Microenvironment
rho-Associated Kinases
/ metabolism
rhoA GTP-Binding Protein
/ metabolism
Biophysical extracellular environment
Cell adhesion
Focal adhesion signalling
MAPK pathway
Ovarian cancer
Rho/ROCK signalling
Journal
Cell biochemistry and biophysics
ISSN: 1559-0283
Titre abrégé: Cell Biochem Biophys
Pays: United States
ID NLM: 9701934
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
accepted:
12
12
2020
pubmed:
13
1
2021
medline:
20
8
2021
entrez:
12
1
2021
Statut:
ppublish
Résumé
It has been long known that the oncogenic extracellular environment plays an indispensable role in developing and nurturing cancer cell progression and in resistance to standard treatments. However, by how much the biophysical components of tumour extracellular environment contribute to these processes is uncertain. In particular, the topographic environment is scarcely explored. The biophysical modulation of cell behaviour is primarily facilitated through mechanotransduction-associated mechanisms, including focal adhesion and Rho/ROCK signalling. Dysregulation of these pathways is commonly observed in ovarian cancer and, therefore, biophysical modulation of these mechanisms may be of great importance to ovarian cancer development and progression. In this work, aspects of the biophysical environment were explored using a bioimprinting technique. The study showed that topography-mediated substrate sensing delayed cell attachment, however, cell-cell interactions overrode the effect of topography in some cell lines, such as OVCAR-5. Also, 3D topographical cues were shown to modulate the inhibition of focal adhesion and Rho signalling, which resulted in higher MAPK activity in cells on the bioimprints. It was revealed that c-Src is vital to the biophysical modulation of cell proliferation and inhibition of c-Src could downregulate biophysically modulated MAPK activity. This study provides evidence that the biophysical extracellular environment affects key intracellular mechanisms associated with tumourigenicity in ovarian cancer cells.
Identifiants
pubmed: 33433760
doi: 10.1007/s12013-020-00964-9
pii: 10.1007/s12013-020-00964-9
doi:
Substances chimiques
Protein Kinase Inhibitors
0
CSK Tyrosine-Protein Kinase
EC 2.7.10.2
Focal Adhesion Kinase 1
EC 2.7.10.2
rho-Associated Kinases
EC 2.7.11.1
MAP Kinase Kinase Kinases
EC 2.7.11.25
rhoA GTP-Binding Protein
EC 3.6.5.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
375-386Références
Cox, T. R., & Erler, J. T. (2011). Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer. Disease Models & Mechanisms, 4(2), 165–178.
Calvo, F., et al. (2013). Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nature Cell Biology, 15(6), 637–646.
pubmed: 23708000
Reid, S. E., et al. (2017). Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO Journal, 36(16), 2373–2389.
Ikeda, S., et al. (2003). Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Human Molecular Genetics, 12(9), 1029–1036.
pubmed: 12700171
Margadant, C., Cremers, L., Sonnenberg, A., & Boonstra, J. (2013). MAPK uncouples cell cycle progression from cell spreading and cytoskeletal organization in cycling cells. Cellular and Molecular Life Sciences, 70(2), 293–307.
pubmed: 22926416
Uroz, M., et al. (2018). Regulation of cell cycle progression by cell-cell and cell-matrix forces. Nature Cell Biology, 20(6), 646–654.
pubmed: 29802405
Keselowsky, B. G., Collard, D. M., & García, A. J. (2004). Surface chemistry modulates focal adhesion composition and signaling through changes in integrin binding. Biomaterials, 25(28), 5947–5954.
pubmed: 15183609
Yim, E. K. F., Darling, E. M., Kulangara, K., Guilak, F., & Leong, K. W. (2010). Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells. Biomaterials, 31(6), 1299–1306.
pubmed: 19879643
Chen, W., Mao, K., Liu, Z., & Dinh-Xuan, A. T. (2014). The role of the RhoA/Rho kinase pathway in angiogenesis and its potential value in prostate cancer (review). Oncology Letters, 8(5), 1907–1911.
pubmed: 25289078
pmcid: 4186560
Cavalcanti-Adam, E. A., Volberg, T., Micoulet, A., Kessler, H., Geiger, B., & Spatz, J. P. (2007). Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophysical Journal, 92(8), 2964–2974.
pubmed: 17277192
pmcid: 1831685
Schiller, H. B., & Fässler, R. (2013). Mechanosensitivity and compositional dynamics of cell-matrix adhesions. EMBO Reports, 14(6), 509–519.
pubmed: 23681438
pmcid: 3674437
Li, M., Hong, L., Liao, M., & Guo, G. (2015). Expression and clinical significance of focal adhesion kinase and adrenomedullin in epithelial ovarian cancer. Oncology Letters, 10(2), 1003–1007.
pubmed: 26622614
pmcid: 4508992
Sulzmaier, F. J., Jean, C., & Schlaepfer, D. D. (2014). FAK in cancer: mechanistic findings and clinical applications. Nature Reviews Cancer, 14(9), 598–610.
pubmed: 25098269
pmcid: 4365862
Stone, R. L., et al. (2014). Focal adhesion kinase: an alternative focus for anti-angiogenesis therapy in ovarian cancer. Cancer Biology & Therapy, 15(7), 919–929.
Huang, Y. W., Chen, C., Xu, M. M., Li, J. D., Xiao, J., & Zhu, X. F. (2013). Expression of c-Src and phospho-Src in epithelial ovarian carcinoma. Molecular and Cellular Biochemistry, 376(1–2), 73–79.
pubmed: 23277333
Xiao, J., Xu, M., Hou, T., Huang, Y., Yang, C., & Li, J. (2015). Dasatinib enhances antitumor activity of paclitaxel in ovarian cancer through Src signaling. Molecular Medicine Reports, 12(3), 3249–3256.
pubmed: 25975261
pmcid: 4526065
Mitra, S. K., Hanson, D. A., & Schlaepfer, D. D. (2005). Focal adhesion kinase: in command and control of cell motility. Nature Reviews Molecular Cell Biology, 6(1), 56–68.
pubmed: 15688067
Croft, D. R., & Olson, M. F. (2006). The Rho GTPase effector ROCK regulates cyclin A, cyclin D1, and p27Kip1 levels by distinct mechanisms. Molecular and Cellular Biology, 26(12), 4612–4627.
pubmed: 16738326
pmcid: 1489131
Peng, X., et al. (2008). Cardiac developmental defects and eccentric right ventricular hypertrophy in cardiomyocyte focal adhesion kinase (FAK) conditional knockout mice. Proceedings of the National Academy of Sciences of the USA, 105(18), 6638–6643.
pubmed: 18448675
Nagy, T., et al. (2007). Mammary epithelial-specific deletion of the focal adhesion kinase gene leads to severe lobulo-alveolar hypoplasia and secretory immaturity of the murine mammary gland. Journal of Biological Chemistry, 282(43), 31766–31776.
Lim, Y., et al. (2008). PyK2 and FAK connections to p190Rho guanine nucleotide exchange factor regulate RhoA activity, focal adhesion formation, and cell motility. Journal of Cell Biology, 180(1), 187–203.
Zhai, J., et al. (2003). Direct interaction of focal adhesion kinase with p190RhoGEF. Journal of Biological Chemistry, 278(27), 24865–24873.
Tan, L. H., Sykes, P. H., Alkaisi, M. M., & Evans, J. J. (2015). The characteristics of ishikawa endometrial cancer cells are modified by substrate topography with cell-like features and the polymer surface. International Journal of Nanomedicine, 10, 4883–4895.
pubmed: 26346435
pmcid: 4531047
Sarwar, M., Sykes, P. H., Chitcholtan, K., Alkaisi, M. M., & Evans, J. J. (2019). The extracellular topographical environment influences ovarian cancer cell behaviour. Biochemical and Biophysical Research Communications, 508(4), 1188–1194.
pubmed: 30558791
Horton, E. R., et al. (2016). Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition. Journal of Cell Biology, 212(3), 349–364.
Ohta, T., et al. (2012). Inhibition of the Rho/ROCK pathway enhances the efficacy of cisplatin through the blockage of hypoxia-inducible factor-1alpha in human ovarian cancer cells. Cancer Biology & Therapy, 13(1), 36–73.
Bolós V., Gasent J. M., López-Tarruella S., & Grande E. (2010). The dual kinase complex Fak-Src as apromising therapeutic target in cancer. Onco Targets and Therapy, 3, 83–97.
Choi, C., Hagvall, S. H., Wu, B. M., Dunn, J. C. Y., Beygui, R. E., & Kim, C. C. J. (2007). Cell interaction with three-dimensional sharp-tip nanotopography. Biomaterials, 28, 1672–1679.
pubmed: 17174392
Lim, J. Y., Hansen, J. C., Siedlecki, C. A., Runt, J., & Donahue, H. J. (2005). Human foetal osteoblastic cell response to polymer-demixed nanotopographic interfaces. Journal of the Royal Society Interface, 2(2), 97–108.
pmcid: 1578253
Pennisi, C. P., et al. (2011). N anoscale topography reduces fibroblast growth, focal adhesion size and migration-related gene expression on platinum surfaces. Colloids and Surfaces B: Biointerfaces, 85(2), 189–197.
pubmed: 21435850
Giannini, M., et al.(2018). Nano-topography: quicksand for cell cycle progression?. Nanomedicine: Nanotechnology, Biology and Medicine, 14(8), 2656–2665.
Tan, L. H., Sykes, P. H., Alkaisi, M. M., & Evans, J. J. (2017). Cell-like features imprinted in the physical nano- and micro-topography of the environment modify the responses to anti-cancer drugs of endometrial cancer cells. Biofabrication, 9(1), 1–10.
Yang, S. P., & Lee, T. M. (2011). The effect of substrate topography on hFOB cell behavior and initial cell adhesion evaluated by a cytodetacher. Journal of Materials Science: Materials in Medicine, 22(4), 1027–1036.
pubmed: 21331605
Seo, C. H., Furukawa, K., Montagne, K., Jeong, H., & Ushida, T. (2011). The effect of substrate microtopography on focal adhesion maturation and actin organization via the RhoA/ROCK pathway. Biomaterials, 32(36), 9568–9575.
pubmed: 21925729
Seo, C. H., Jeong, H., Furukawa, K. S., Suzuki, Y., & Ushida, T. (2013). The switching of focal adhesion maturation sites and actin filament activation for MSCs by topography of well-defined micropatterned surfaces. Biomaterials, 34(7), 1764–1771.
pubmed: 23219606
Lunova, M., et al. (2016). Modulation of collective cell behaviour by geometrical constraints. Integrative Biology, 8(11), 1099–1110.
pubmed: 27738682
Wang, X., Jiang, W., Kang, J., Liu, Q., & Nie, M. (2015). Knockdown of RhoA expression alters ovarian cancer biological behavior in vitro and in nude mice. Oncology Reports, 34(2), 891–899.
pubmed: 26035556
Schulte, C., et al. (2016). Conversion of nanoscale topographical information of cluster-assembled zirconia surfaces into mechanotransductive events promotes neuronal differentiation. Journal of Nanobiotechnology, 14(1), 1–24.
Dalby, M. J., Gadegaard, N., & Oreffo, R. O. C. (2014). Harnessing nanotopography and integrin-matrix interactions to influence stem cell fate. Nature Materials, 13(6), 558–569.
pubmed: 24845995
Marlowe, T. A., Lenzo, F. L., Figel, S. A., Grapes, A. T., & Cance, W. G. (2016). Oncogenic receptor tyrosine kinases directly phosphorylate focal adhesion kinase (FAK) as a resistance mechanism to FAK-kinase inhibitors. Molecular Cancer Therapeutics, 15(12), 3028–3039.
pubmed: 27638858
pmcid: 5136315
Hamilton, D. W., & Brunette, D. M. (2007). The effect of substratum topography on osteoblast adhesion mediated signal transduction and phosphorylation. Biomaterials, 28(10), 1806–1819.
pubmed: 17215038
Brasseur, K., Gévry, N., & Asselin, E. (2017). Chemoresistance and targeted therapies in ovarian and endometrial cancers. Oncotarget, 8(3), 4008–4042.
pubmed: 28008141
Nakashima, M., et al. (2011). Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells. Molecular Cancer, 10, 1–11.
Nakashima, M., Adachi, S., Yasuda, I., Yamauchi, T., Kozawa, O., & Moriwaki, H. (2010). Rho-kinase regulates negatively the epidermal growth factor-stimulated colon cancer cell proliferation. International Journal of Oncology, 36(6), 585–592.
pubmed: 20126978
Evans, J. J., Alkaisi, M. M., & Sykes, P. H. (2019). Tumour initiation: a discussion on evidence for a ‘load-trigger’ mechanism. Cell Biochemistry and Biophysics, 77(4), 293–308.
pubmed: 31598831
pmcid: 6841748