Oncotarget

Research Papers:

Implication of integrin α2β1 in anoikis of SK-Mel-147 human melanoma cells: a non-canonical function of Akt protein kinase

Nadezhda I. Kozlova, Galina E. Morozevich, Natalia A. Ushakova and Albert E. Berman _

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Oncotarget. 2019; 10:1829-1839. https://doi.org/10.18632/oncotarget.26746

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Abstract

Nadezhda I. Kozlova1, Galina E. Morozevich1, Natalia A. Ushakova1 and Albert E. Berman1

1VN Orekhovich Institute of Biomedical Chemistry, Moscow, Russia

Correspondence to:

Albert E. Berman, email: 1938berman@gmail.com

Keywords: integrins, α2β1, anoikis, tumor growth, Akt isoforms

Received: December 12, 2018     Accepted: February 15, 2019     Published: March 05, 2019

ABSTRACT

Suppression of anoikis, a kind of apoptosis caused by disruption of contacts between cell and extracellular matrix, is an important prerequisite for cancer cell metastasis. In this communication, we demonstrate that shRNA-mediated depletion of α2 integrin subunit induces anoikis and substantially decreases colony-forming potential in SK-Mel-147 human melanoma cells. Suppression of α2β1 upregulates the levels of pro-apoptotic protein p53 and cyclin-dependent kinase inhibitors p21 and p27. Concomitantly, we detected decrease in the levels of anti-apoptotic protein Bcl-2 and cell cycle regulator c-Myc. Moreover, depletion of α2β1 reduces the activity of protein kinase Erk, while increases activity of Akt kinase. Pharmacological inhibition of P3IK kinase, an upstream activator of Akt, greatly enhanced anoikis in control cells while reduced that in cells with decreased levels of α2β1. Of three isoforms of Akt, down-regulation of Akt1 greatly diminished anoikis of cells depleted of α2β1, while down-regulation of Akt2 and Akt3 sharply increased anoikis in these cells. These findings were supported by the data of pharmacological inhibition of the Akt isoforms. Our results demonstrate for the first time that anoikis induced by α2β1 integrin knockdown can be attenuated by Akt1 inhibition.


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