Anoikis molecular pathways and its role in cancer progression

Abstract

Anoikis is a programmed cell death induced upon cell detachment from extracellular matrix, behaving as a critical mechanism in preventing adherent-independent cell growth and attachment to an inappropriate matrix, thus avoiding colonizing of distant organs. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are vital steps during cancer progression and metastatic colonization, the ability of cancer cells to resist anoikis has now attracted main attention from the scientific community. Cancer cells develop anoikis resistance due to several mechanisms, including change in integrins' repertoire allowing them to grow in different niches, activation of a plethora of inside-out pro-survival signals as over-activation of receptors due to sustained autocrine loops, oncogene activation, growth factor receptor overexpression, or mutation/upregulation of key enzymes involved in integrin or growth factor receptor signaling. In addition, tumor microenvironment has also been acknowledged to contribute to anoikis resistance of bystander cancer cells, by modulating matrix stiffness, enhancing oxidative stress, producing pro-survival soluble factors, triggering epithelial-mesenchymal transition and self-renewal ability, as well as leading to metabolic deregulations of cancer cells. All these events help cancer cells to inhibit the apoptosis machinery and sustain pro-survival signals after detachment, counteracting anoikis and constituting promising targets for anti-metastatic pharmacological therapy. This article is part of a Special Section entitled: Cell Death Pathways.

Definições E Mecanismos Moleculares Em Morte Celular

“…A indução da cascata de morte celular ocorre através da interação de duas vias apoptóticas, ou seja, a via das mitocôndrias (via intrínseca) ou a ativação dos receptores de morte da superfície celular (via extrínseca). As proteínas da família BCL-2 são os principais atuantes em ambas as vias (PAOLI et al 2013).…”

“…As células tumorais desenvolvem rapidamente vários mecanismos para resistir à anoikis, espalhando metástases para órgãos distantes. Essas células buscam a resistência por diferentes modos: promovendo mudança específica em suas integrinas, impedindo a ligação dos receptores e adaptando-se ao sítio metastático; realizando a transição do epitélio mesenquimal; ativando uma cascata pró-sobrevivência a fatores intrínsecos e ambientais; e ainda, desregulamentando e adaptando o metabolismo, principalmente pela realização da autofagia (PAOLI et al 2013). …”

Correlation between E-Cadherin-Regulated Cell Adhesion and Human Osteosarcoma MG-63 Cell Anoikis

“…Studies have shown that when cells detach from the matrix and become aggregated, the cells can escape anoikis by intercellular signaling, which mimics cell-matrix signal transduction (Ivanova et al, 2013;Paoli et al, 2013). Aggregation is also believed to enhance their resistance to chemotherapeutic drugs.…”

Molecular mechanism of peritoneal dissemination in gastric cancer

“…HIF1α also induces angiopoietin-like-4 (ANGPTL4), a secreted protein essential for tumor growth and resistance to anoikis in GC cells [44] . Cancer cells develop anoikis resistance via several mechanisms, including changes in integrin repertoire expression, induction of EMT, oncogene activation, and adaption of their metabolism [45][46][47] . In gastrointestinal cancers, the PI3K/Akt [48][49][50] and PTEN/PI3K/NF-κB/FAK pathways [51,52] are involved in the formation of PD and anoikis resistance.…”