Panchbhai Neha, Turaga Ravi Chakra, Sharma Malvika, Satyanarayana Ganesh, Liu Zhi-Ren
Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
J Cancer. 2021 Sep 9;12(21):6543-6552. doi: 10.7150/jca.61505. eCollection 2021.
Aberrant expression of P68 RNA helicase (p68), a prototypical member of the DEAD box family of RNA helicases, contributes to tumor development and progression. P68 tyrosine phosphorylation induced by PDGF signaling facilitates cancer metastasis by promoting EMT. In this report, we show that p68 promotes breast cancer cell EMT and cell migration by upregulation of PDGF receptor β (PDGFR-β). Knockdown of p68 in MDA-MB-231 and BT549 cells significantly decreases PDGFR-β both in mRNA and protein levels. P68 promotes EMT and cell migration in response to PDGF-BB stimulation via upregulation of PDGFR-β, suggesting that p68 enhances PDGF signaling by a positive feedback loop in cancer cells. Furthermore, our study reveals that p68 mediates the effects of PDGFR-β in regulation of androgen receptor (AR) in breast cancer cells. We demonstrate that p68 and PDGFR-β co-regulate AR expression and promote androgen-mediated proliferation in breast cancer cells. Our studies uncover an important pathway of p68-PDGFR-β axis in promoting breast cancer progression.
P68 RNA解旋酶是RNA解旋酶DEAD盒家族的典型成员，其异常表达促进肿瘤的发生和发展。血小板衍生生长因子（PDGF）信号诱导的P68酪氨酸磷酸化通过促进上皮-间质转化（EMT）来推动癌症转移。在本报告中，我们发现p68通过上调血小板衍生生长因子受体β（PDGFR-β）来促进乳腺癌细胞的EMT和细胞迁移。在MDA-MB-231和BT549细胞中敲低p68会显著降低PDGFR-β的mRNA和蛋白质水平。p68通过上调PDGFR-β响应PDGF-BB刺激促进EMT和细胞迁移，这表明p68通过癌细胞中的正反馈环增强PDGF信号。此外，我们的研究表明p68在乳腺癌细胞中介导PDGFR-β对雄激素受体（AR）的调控作用。我们证明p68和PDGFR-β共同调节AR表达并促进雄激素介导的乳腺癌细胞增殖。我们的研究揭示了p68-PDGFR-β轴在促进乳腺癌进展中的重要途径。
