title: Topography induces differential sensitivity on cancer cell proliferation via Rho-ROCK-Myosin contractility.
abstract: Although the role of stiffness on proliferative response of cancer cells has been well studied, little is known about the effect of topographic cues in guiding cancer cell proliferation. Here, we examined the effect of topographic cues on cancer cell proliferation using micron scale topographic features and observed that anisotropic features like microgratings at specific dimension could reduce proliferation of non-cancer breast epithelial cells (MCF-10A) but not that for malignant breast cancer cells (MDA-MB-231 and MCF-7). However, isotropic features such as micropillars did not affect proliferation of MCF-10A, indicating that the anisotropic environmental cues are essential for this process. Interestingly, acto-myosin contraction inhibitory drugs, Y-27632 and blebbistatin prevented micrograting-mediated inhibition on proliferation. Here, we propose the concept of Mechanically-Induced Dormancy (MID) where topographic cues could activate Rho-ROCK-Myosin signaling to suppress non-cancerous cells proliferation whereas malignant cells are resistant to this inhibitory barrier and therefore continue uncontrolled proliferation.
authors.affiliation: Mechanobiology Institute, National University of Singapore, SINGAPORE.
authors.forename: Parthiv Kant
authors.initials: PK
authors.lastname: Chaudhuri
authors.affiliation: Mechanobiology Institute, National University of Singapore, SINGAPORE.
authors.forename: Catherine Qiurong
authors.initials: CQ
authors.lastname: Pan
authors.affiliation: Mechanobiology Institute, National University of Singapore, SINGAPORE.|Cell Signaling and Developmental Biology Laboratory, Department of Biological Sciences, National University of Singapore, SINGAPORE.
authors.forename: Boon Chuan
authors.initials: BC
authors.lastname: Low
authors.affiliation: Mechanobiology Institute, National University of Singapore, SINGAPORE.|Department of Biomedical Engineering, National University of Singapore, SINGAPORE.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002417:Cattle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006801:Humans; D009218:Myosins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D003094:Collagen; D054460:rho-Associated Kinases; D009218:Myosins; D020741:rho GTP-Binding Proteins