αB-crystallin induces by matrix detachment via ERK is critical in inhibition of anoikis


Anoikis, extracellular matrix detachment-induced apoptosis, plays a critical role in maintaining tissue structure by eliminating epithelial cells that have been displaced from their extracellular matrix. The resistance of anoikis is a defining characteristic of metastatic carcinoma cells. Malin et al. identified an matrix detachment-induced antiapoptotic molecular chaperone, αB-crystallin, confers anoikis resistance. The article was published in Oncogene.


Researchers found matrix detachment suppress activity of extracellular signal-regulated kinase (ERK) and increases αB-crystallin protein and messenger RNA (mRNA) levels. In addition, they found ERK signaling negatively correlated with αB-crystallin protein and mRNA levels, indicating ERK inhibition is both necessary and sufficient for αB-crystallin induction. Furthermore, by silencing αB-crystallin in two different matastatic carcinoma cell lines, they observed an increase of matrix detachment-induced caspase activation and apoptosis, as well as a reduction of viable circulating tumor cells, but did not affect viability of adherent cancer cells and primary tumor growth. The findings suggested that αB-crystallin works as a novel regulator of anoikis resistance and a promising therapeutic target against tumor metastasis.


Oncogene. 2015 Feb 16. doi: 10.1038/onc.2015.12. 

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