title: Force-dependent breaching of the basement membrane.
abstract: Clinically, non-invasive carcinomas are confined to the epithelial side of the basement membrane and are classified as benign, whereas invasive cancers invade through the basement membrane and thereby acquire the potential to metastasize. Recent findings suggest that, in addition to protease-mediated degradation and chemotaxis-stimulated migration, basement membrane invasion by malignant cells is significantly influenced by the stiffness of the associated interstitial extracellular matrix and the contractility of the tumor cells that is dictated in part by their oncogenic genotype. In this review, we highlight recent findings that illustrate unifying molecular mechanisms whereby these physical cues contribute to tissue fibrosis and malignancy in three epithelial organs: breast, pancreas, and liver. We also discuss the clinical implications of these findings and the biological properties and clinical challenges linked to the unique biology of each of these organs.
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Liver Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: tammy.chang@ucsf.edu.
authors.forename: Tammy T
authors.initials: TT
authors.lastname: Chang
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: dhruv.thakar@ucsf.edu.
authors.forename: Dhruv
authors.initials: D
authors.lastname: Thakar
authors.affiliation: Department of Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Center for Bioengineering and Tissue Regeneration, University of California San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, UCSF, San Francisco, CA 94143, USA; Department of Bioengineering and Therapeutic Sciences, UCSF, San Francisco, CA 94143, USA; Department of Radiation Oncology, UCSF, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, UCSF, San Francisco, CA 94143, USA; The Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA 94143, USA. Electronic address: Valerie.Weaver@ucsf.edu.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Weaver
mesh_terms: D001485:Basement Membrane / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002633:Chemotaxis; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013314:Stress, Mechanical
chemical_list: D007797:Laminin; D003094:Collagen
keywords: Breast cancer; Hepatocellular carcinoma; Matrix rigidity; Pancreatic cancer; Tumor invasion