TY - JOUR
T1 - α v β 3 integrin mediates radioresistance of prostate cancer cells through regulation of survivin
AU - Wang, Tao
AU - Huang, Jiayi
AU - Vue, Mai
AU - Alavian, Michael R.
AU - Goel, Hira Lal
AU - Altieri, Dario C.
AU - Languino, Lucia R.
AU - FitzGerald, Thomas J.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060911818&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-18-0544
DO - 10.1158/1541-7786.MCR-18-0544
M3 - Article
C2 - 30266752
AN - SCOPUS:85060911818
SN - 1541-7786
VL - 17
SP - 398
EP - 408
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 2
ER -