Anoikis Resistance: An Essential Prerequisite for Tumor Metastasis

Abstract

Metastasis is a multistep process including dissociation of cancer cells from primary sites, survival in the vascular system, and proliferation in distant target organs. As a barrier to metastasis, cells normally undergo an apoptotic process known as “anoikis,” a form of cell death due to loss of contact with the extracellular matrix or neighboring cells. Cancer cells acquire anoikis resistance to survive after detachment from the primary sites and travel through the circulatory and lymphatic systems to disseminate throughout the body. Because recent technological advances enable us to detect rare circulating tumor cells, which are anoikis resistant, currently, anoikis resistance becomes a hot topic in cancer research. Detailed molecular and functional analyses of anoikis resistant cells may provide insight into the biology of cancer metastasis and identify novel therapeutic targets for prevention of cancer dissemination. This paper comprehensively describes recent investigations of the molecular and cellular mechanisms underlying anoikis and anoikis resistance in relation to intrinsic and extrinsic death signaling, epithelial-mesenchymal transition, growth factor receptors, energy metabolism, reactive oxygen species, membrane microdomains, and lipid rafts.

IRX1 hypomethylation promotes osteosarcoma metastasis via induction of CXCL14/NF-κB signaling

“…As expected, higher IRX1 mRNA expression was detected in the highly metastatic 143B cells relative to the mRNA levels in MNNG-HOS cells ( Figure 1B). Accordingly, IRX1 protein levels were also substantially upregulated in ZOSM and 143B cells, as indicated by Western blot and immunofluorescence analyses ( Figure 1C anoikis is a physiological barrier to metastasis and that resistance to anoikis may facilitate distant organ metastasis (24,25), we further examined the effect of IRX1 deletion on the anoikis of osteosarcoma cells by culturing cells on ultra-low attachment plates. After a 48-hour incubation, we found that ZOSM-shIRX1 and 143B-shIRX1 cells were more sensitive to detachment-induced apoptosis than were their scrambled controls ( Figure 3D).…”

Antioxidant Enzymes Mediate Survival of Breast Cancer Cells Deprived of Extracellular Matrix

“…As such, tumor cells require resistance to anoikis to survive during cancer progression (4,5). The ability to evade anoikis is critically important during the metastatic cascade, as cancer cells are forced to survive in the absence of ECM-attachment while in the blood or lymphatic vessels.…”

The protein phosphatase 4 - PEA15 axis regulates the survival of breast cancer cells

“…Further analysis has confirmed the interaction between PP4c and PEA15 and demonstrates that PP4c -induced apoptosis in normal lymphocytes and T-leukemic cells is partly mediated through the direct or indirect dephosphorylation of PEA15 [23]. PEA15 is a member of the death effector domain (DED) protein family known to regulate cell proliferation, autophagy, and apoptosis [28,29]. It is implicated in the dysregulation of many signalling pathways involved in cancer progression and tumorigenesis and it has been described to act as both a tumour suppressor and a tumour promoter, dependent on its phosphorylation status [30][31][32].…”