Springer Anoikis: How the Extracellular Matrix Regulates Life-or-Death Decisions

Anoikis is defined broadly as apoptosis that is inhibited by appropriate cell-matrix interactions.  Normal and tumor cells vary widely in their sensitivity to anoikis, but, in general, metastatic tumor cells are inevitably anoikis-resistant.  In particular, tumor cells that possess a cancer stem cell or mesenchymal phenotype, arising from the oncogenic Epithelial-Mesenchymal Transition (EMT), are transcriptionally re-programmed to resist anoikis.  While the anoikis response occurs through the mitochondrial pathway typically found in other apoptotic responses (e.g., DNA damage, death receptors, oxidative stress), the regulation of anoikis by cell-matrix signalling is unique and only partially characterized.  The uniqueness of anoikis is: a. regulation by integrins, non-integrin matrix receptors, and the signaling complexes associated with them; b. regulation by metabolic changes occurring in response to attachment/detachment;  c. regulation by oncogenes and tumor suppressor genes d. regulation by tumor microenvironment;  e. regulation by EMT. From the Back Cover This book provides a useful resource for graduate-level cancer cell biology courses. Since the first report, in 1994, of “anoikis”―the apoptosis that occurs when cells lack appropriate contact with the extracellular matrix―over 2,100 papers have been published on this subject. This book is the first comprehensive, in-depth and up-to-date compendium on anoikis. Chapters are authored by some of the leading researchers in the field. This book provides both mechanistic and translational information regarding anoikis, in a convenient format.  Mechanistically, the following topics will be addressed in detail:  The role of MAP kinase signaling  The role of Shc proteins as cellular anchorage sensors  The role of cellular metabolism, and fatty acid metabolism in particular,  and how they are affected by oncogenic transformation  How epithelial cell extrusion – the prelude to anoikis―is regulated in normal and cancer cells The convergence of TGF-b and androgen receptor signaling in the regulation of anoikis  This book also discusses the specialized functions and dysregulation of anoikis in the following cancer settings:  Colon cancer  Melanoma  Cervical cancer  The book serves to update i nvestigators actively working on problems in the anoikis field, in either experimental or translational settings. For investigators encountering novel biological phenomena that might relate to anoikis, it serve as an entry point to the literature that does not require an extensive background in cell adhesion signaling or apoptosis mechanisms.    About the Author Steven M. Frisch received his Ph.D. in Biochemistry from the University of California, Berkeley (where he worked with Dr. Zena Werb, at U.C.S.F). Following postdoctoral training at the M.I.T. Center for Cancer Research, Dr. Frisch served on the faculties of Washington University, St. Louis and the Sanford-Burnham-Prebys Institute, and is currently a Professor of Biochemistry at West Virginia University. Dr. Frisch has published extensively in the area of cancer cell biology and is internationally recognized for his important contributions to the field.