Show simple item record

dc.contributor.authorWang, Tao
dc.contributor.authorHuang, Jiayi
dc.contributor.authorVue, Mai
dc.contributor.authorAlavian, Michael R.
dc.contributor.authorGoel, Hira Lal
dc.contributor.authorAltieri, Dario C.
dc.contributor.authorLanguino, Lucia R.
dc.contributor.authorFitzgerald, Thomas J.
dc.date2022-08-11T08:10:45.000
dc.date.accessioned2022-08-23T17:18:39Z
dc.date.available2022-08-23T17:18:39Z
dc.date.issued2019-02-01
dc.date.submitted2019-01-16
dc.identifier.citation<p>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. <a href="https://doi.org/10.1158/1541-7786.MCR-18-0544">Link to article on publisher's site</a></p>
dc.identifier.issn1541-7786 (Linking)
dc.identifier.doi10.1158/1541-7786.MCR-18-0544
dc.identifier.pmid30266752
dc.identifier.urihttp://hdl.handle.net/20.500.14038/47900
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=30266752&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359981/
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectCancer Biology
dc.subjectNeoplasms
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectOncology
dc.subjectRadiation Medicine
dc.subjectRadiology
dc.subjectTherapeutics
dc.titlealphavbeta3 Integrin Mediates Radioresistance of Prostate Cancer Cells Through Regulation of Survivin
dc.typeJournal Article
dc.source.journaltitleMolecular cancer research : MCR
dc.source.volume17
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/radiationoncology_pubs/100
dc.identifier.contextkey13633540
html.description.abstract<p>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.</p> <p>Implications: Future translational research on targeting alphavbeta3 integrin and survivin may reveal novel approaches as an adjunct to radiotherapy for patients with prostate cancer.</p>
dc.identifier.submissionpathradiationoncology_pubs/100
dc.contributor.departmentDepartment of Molecular, Cell and Cancer Biology
dc.contributor.departmentDepartment of Radiation Oncology
dc.source.pages398-408


This item appears in the following Collection(s)

Show simple item record