The sensors and regulators of cell–matrix surveillance in anoikis resistance of tumors

Abstract

Normal cells continuously monitor the nature of their respective cellular microenvironment. They are equipped with an inherent molecular defense to detect changes which can precipitate and trigger an oncogenic cascade in the internal and external environment of cells. The process called Anoikis unleashes many a characteristic molecular changes in cells which eventually program to cell death in response to cell detachment and inappropriate cellular attachment, both of which can otherwise potentiate the ability of cells to preferentially pursue a malignant course due to release of molecular discipline which conforms them to a benign structural and functional spectrum. The initiation and propagation of signaling which serves as a switch to cell survival or cell death mediated by surveillance of cell microenvironment is comprised of many heterogeneous sets of molecules interacting mainly at the interface of cell-extracellular matrix. Transforming cells continuously reprogram their signaling characteristics in sensing and modulating the stimuli from cell surface molecules like integrins, cadherins and immunoglobulin family of cell adhesion molecules at adhesion complexes which enables them to resist anoikis and metastasize to different organs. Actin cytoskeleton binds BIM and BMF which are regulated by the adhesion status and consequent conformation of cytoskeleton in the cells. This review aims at an integrated synopsis of fundamental mechanisms of the critical interactions of cell surface molecules to facilitate a focused analysis of differential regulation of signaling processes at cell-ECM junctions that collectively rein the anoikis resistance which in turn impacts metastatic aggressiveness and drug-resistance of tumors originating from respective organs.

Telomerase promotes efficient cell cycle kinetics and confers growth advantage to telomerase-negative transformed human cells

“…Additionally, TERT has recently been shown to function as a transcriptional coactivator of the b-catenin transcriptional complex in mice (Park et al, 2009). As anoikis can be reversed by the acquisition of anchorage independence or cell motilityrelated factors (Nagaprashantha et al, 2011), the expression levels of these cellular proteins could be measured in ALT cells before and after telomerase replacement. Our laboratory is actively pursuing this line of work.…”

Olfactomedin III expression contributes to anoikis-resistance in clonal variants of a human lung squamous carcinoma cell line

“…This is not surprising as changes in apoptosis and/or autophagy may result in anoikis resistance. For apoptosis, many sets of molecules interact at the cell surface, inducing different downstream signalling cascades that lead to intracellular machinery controlling apoptosis [43]. In addition, the signalling molecules connecting the cytoskeleton and cytoplasm to the extracellular matrix can exhibit extensive cross-talk between the different signalling pathways [44].…”

Modified Yi Guan Jian, a Chinese herbal formula, induces anoikis in Bel-7402 human hepatocarcinoma cells in vitro

“…There is a growing consensus that lack of signalling through the MAPK/ERK pathway, through loss of integrinmediated contact with the extracellular matrix, contributes to anoikis (22,24,(28)(29)(30). Integrins, the main cell surface receptors 'sense' adhesion to the extracellular matrix, triggering an intracellular signaling cascade via focal adhesion kinase (FAK) and other kinases, leading to activation of the MAP kinases.…”