α v β 3 integrin mediates radioresistance of prostate cancer cells through regulation of survivin

Tao Wang, Jiayi Huang, Mai Vue, Michael R. Alavian, Hira Lal Goel, Dario C. Altieri, Lucia R. Languino, Thomas J. FitzGerald

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The α v β 3 integrin is involved in various physiologic and pathologic processes such as wound healing, angiogenesis, tumor growth, and metastasis. The impact of α v β 3 integrin on the radiosensitivity of prostate cancer cells and the molecular mechanism controlling cell survival in response to ionizing radiation (IR) was investigated. Both LNCaP cells stably transfected with α v β 3 integrin and PC-3 cells that contain endogenous β3 integrin were used. This study demonstrated that α v β 3 integrin increases survival of α v β 3 -LNCaP cells upon IR while small hairpin RNA (shRNA)-mediated knockdown of α v β 3 integrin in PC-3 cells sensitizes to radiation. Expression of α v β 3 integrin in LNCaP cells also enhances anchorageindependent cell growth while knockdown of α v β 3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The avb3 antagonist, cRGD, significantly increases radiosensitivity in both α v β 3 -LNCaP and PC-3 cells. Moreover, α v β 3 integrin prevents radiation-induced downregulation of survivin. Inhibition of survivin expression by siRNA or shRNA enhances IR-induced inhibition of anchorage-independent cell growth. Overexpression of wild-type survivin in PC-3 cells treated with α v β 3 integrin shRNA increases survival of cells upon IR. These findings reveal that α v β 3 integrin promotes radioresistance and regulates survivin levels in response to IR. Implications: Future translational research on targeting α v β 3 integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.

Original languageEnglish
Pages (from-to)398-408
Number of pages11
JournalMolecular Cancer Research
Volume17
Issue number2
DOIs
StatePublished - Feb 2019

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