Yang P, Liang S-X, Huang W-H, Zhang H-W, Li X-L, Xie L-H, Du C-W, Zhang G-J
(C.-W. Du) Department of Breast Medical Oncology, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou 515031, P.R. China.
Curr Mol Med. 2014 Jan;14(1):174-84. doi: 10.2174/1566524013666131121115656.
Triple negative breast cancer is known for its visceral metastasis. We have found that CXCR4 is overexpressed in triple negative breast cancer and is associated with visceral metastasis. We further investigated whether CXCR4 is a prognostic factor affecting survival following visceral metastasis in breast cancer patients. Our results indicate that increased CXCR4 expression among breast cancer patients with visceral metastasis was positively correlated with poor overall survival (P<0.001). Silencing of CXCR4 was associated with a decrease in the tumorigenic properties of MDA-MB-231 breast cancer cells, caused reversion of EMT and suppression of MMP-9, increased apoptosis, and caused a reduced incidence of tumor lung metastasis in mice. These results are indicative of CXCR4 having a predictive role in patients with visceral metastasis and indicate that shRNA knock down of CXCR4 might be a novel therapeutic strategy to prevent breast cancer metastasis when CXCR4 is overexpressed.
三阴性乳腺癌以其内脏转移而闻名。我们发现CXCR4在三阴性乳腺癌中过度表达，且与内脏转移相关。我们进一步研究了CXCR4是否是影响乳腺癌患者内脏转移后生存的预后因素。我们的结果表明，内脏转移的乳腺癌患者中CXCR4表达增加与总体生存率差呈正相关（P<0.001）。CXCR4的沉默与MDA-MB-231乳腺癌细胞致瘤特性的降低相关，导致上皮-间质转化逆转和基质金属蛋白酶-9的抑制，增加细胞凋亡，并使小鼠肿瘤肺转移的发生率降低。这些结果表明CXCR4在内脏转移患者中具有预测作用，并表明当CXCR4过度表达时，CXCR4的短发夹RNA敲低可能是预防乳腺癌转移的一种新的治疗策略。
