Overcoming anoikis – pathways to anchorage-independent growth in cancer

Abstract

SummaryAnoikis (or cell-detachment-induced apoptosis) is a self-defense strategy that organisms use to eliminate 'misplaced' cells, i.e. cells that are in an inappropriate location. Occasionally, detached or misplaced cells can overcome anoikis and survive for a certain period of time in the absence of the correct signals from the extracellular matrix (ECM). If cells are able to adapt to their new environment, then they have probably become anchorage-independent, which is one of the hallmarks of cancer cells. Anoikis resistance and anchorage-independency allow tumor cells to expand and invade adjacent tissues, and to disseminate through the body, giving rise to metastasis. Thus, overcoming anoikis is a crucial step in a series of changes that a tumor cell undergoes during malignant transformation.Tumor cells have developed a variety of strategies to bypass or overcome anoikis. Some strategies consist of adaptive cellular changes that allow the cells to behave as they would in the correct environment, so that induction of anoikis is aborted. Other strategies aim to counteract the negative effects of anoikis induction by hyperactivating survival and proliferative cascades. The recently discovered processes of autophagy and entosis also highlight the contribution of these mechanisms to rendering the cells in a dormant state until they receive a signal initiated at the ECM, thereby circumventing anoikis. In all situations, the final outcome is the ability of the tumor to grow and metastasize. A better understanding of the mechanisms underlying anoikis resistance could help to counteract tumor progression and prevent metastasis formation.

miR-125a inhibits the migration and invasion of liver cancer cells via suppression of the PI3K/AKT/mTOR signaling pathway

“…In the present study, soft agar and Transwell assays were used to validate the role of miR-125a in regulating the proliferation and migration of liver cancer cells. A soft agar colony formation assay may be used to monitor tumor anchorage-independence growth and tumor malignancy, where a stronger invasion ability of tumor cells is associated with a greater number of cell colonies (24,26,27). Tumor migration and invasion ability is dependent on the microenvironment for growth and the extracellular matrix (ECM), therefore a Transwell chamber model that imitates the ECM represents a reliable method for assaying cell invasion ability (28).…”

The metastatic cancer cell cortex: An adaptation to enhance robust cell division in novel environments?

“…Most non-transformed cells rely on constant adhesionbased signaling for their continued survival and proliferation, both through cell-cell contacts and through integrinmediated adhesion to the extra-cellular matrix (ECM). Thus, when grown in a soft, non-adhesive environment, where such signals are lacking, cells enter a cell cycle arrest [3] or undergo death by a process termed anoikis [4]. Cancer cells are known to use a wide range of mechanisms to overcome this dependence on local signals for survival and proliferation [5].…”

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

“…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].…”