alphavbeta3 Integrin Mediates Radioresistance of Prostate Cancer Cells Through Regulation of Survivin
Authors
Wang, TaoHuang, Jiayi
Vue, Mai
Alavian, Michael R.
Goel, Hira Lal
Altieri, Dario C.
Languino, Lucia R.
Fitzgerald, Thomas J.
UMass Chan Affiliations
Department of Molecular, Cell and Cancer BiologyDepartment of Radiation Oncology
Document Type
Journal ArticlePublication Date
2019-02-01Keywords
Amino Acids, Peptides, and ProteinsCancer Biology
Neoplasms
Nucleic Acids, Nucleotides, and Nucleosides
Oncology
Radiation Medicine
Radiology
Therapeutics
Metadata
Show full item recordAbstract
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.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
DOI
10.1158/1541-7786.MCR-18-0544Permanent Link to this Item
http://hdl.handle.net/20.500.14038/47900PubMed ID
30266752Related Resources
ae974a485f413a2113503eed53cd6c53
10.1158/1541-7786.MCR-18-0544