Title

alphavbeta3 Integrin Mediates Radioresistance of Prostate Cancer Cells Through Regulation of Survivin

UMMS Affiliation

Department of Radiation Oncology; Department of Molecular, Cell and Cancer Biology

Publication Date

2019-02-01

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cancer Biology | Neoplasms | Nucleic Acids, Nucleotides, and Nucleosides | Oncology | Radiation Medicine | Radiology | Therapeutics

Abstract

The alphavbeta3 integrin is involved in various physiologic and pathologic processes such as wound healing, angiogenesis, tumor growth, and metastasis. The impact of alphavbeta3 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 alphavbeta3 integrin and PC-3 cells that contain endogenous beta3 integrin were used. This study demonstrated that alphavbeta3 integrin increases survival of alphavbeta3-LNCaP cells upon IR while small hairpin RNA (shRNA)-mediated knockdown of alphavbeta3 integrin in PC-3 cells sensitizes to radiation. Expression of alphavbeta3 integrin in LNCaP cells also enhances anchorage-independent cell growth while knockdown of alphavbeta3 integrin in PC-3 cells inhibits anchorage-independent cell growth. The alphavbeta3 antagonist, cRGD, significantly increases radiosensitivity in both alphavbeta3-LNCaP and PC-3 cells. Moreover, alphavbeta3 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 alphavbeta3 integrin shRNA increases survival of cells upon IR. These findings reveal that alphavbeta3 integrin promotes radioresistance and regulates survivin levels in response to IR.

Implications: Future translational research on targeting alphavbeta3 integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.

DOI of Published Version

10.1158/1541-7786.MCR-18-0544

Source

Mol Cancer Res. 2019 Feb;17(2):398-408. doi: 10.1158/1541-7786.MCR-18-0544. Epub 2018 Sep 28. PMID: 30266752; PMCID: PMC6359981. Link to article on publisher's site

Journal/Book/Conference Title

Molecular cancer research : MCR

Related Resources

Link to Article in PubMed

PubMed ID

30266752

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