Hypoxia inducible factor-1α-dependent epithelial to mesenchymal transition under hypoxic conditions in prostate cancer cells.
Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death. Hypoxia is an environmental stimulus that plays an important role in the development and cancer progression especially for solid tumors. The key regulator under hypoxic conditions is stabilized hypoxia-inducible factor (HIF)-1α. In the present study, immune-fluorescent staining, siRNAs, qRT-PC, immunoblotting, cell migration and invasion assays were carried out to test typical epithelial to mesenchymal transition under hypoxia and the key regulators of this process in PC3, a human prostate cancer cell line. Our data demonstrated that hypoxia induces diverse molecular, phenotypic and functional changes in prostate cancer cells that are consistent with EMT. We also showed that a cell signal factor such as HIF-1α, which might be stabilized under hypoxic environment, is involved in EMT and cancer cell invasive potency. The induced hypoxia could be blocked by HIF-1α gene silencing and reoxygenation of EMT in prostate cancer cells, hypoxia partially reversed accompanied by a process of mesenchymal-epithelial reverting transition (MErT). EMT might be induced by activation of HIF-1α-dependent cell signaling in hypoxic prostate cancer cells.
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
Mingchuan
M
Li
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
Yong Xing
YX
Wang
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
Yong
Y
Luo
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
Jiahui
J
Zhao
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
Qing
Q
Li
Department of Anatomy and Cell Biology, East Carolina University, Greenville, NC 27834, USA.
Jiao
J
Zhang
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China.
Yongguang
Y
Jiang
D015687:Cell Hypoxia / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008297:Male; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit