降低let-7g表达对乳腺癌的侵袭转移起着重要作用

Cancer Res 2011 Oct;71(20):6463-74. [IF:8.234]

Pivotal role of reduced let-7g expression in breast cancer invasion and metastasis.

Qian P , Zuo Z , Wu Z , Meng X , Li G , Wu Z , Zhang W , Tan S , Pandey V , Yao Y , Wang P , Zhao L , Wang J , Wu Q , Song E , Lobie PE , Yin Z , Zhu T .

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.

中国科学技术大学合肥微尺度物质科学国家实验室

Abstract

Screening of the entire let-7 family of microRNAs (miRNA) by in situ hybridization identified let-7g as the only member, the diminished expression of which was significantly associated with lymph node metastasis and poor survival in breast cancer patients. Abrogation of let-7g expression in otherwise nonmetastatic mammary carcinoma cells elicited rapid metastasis from the orthotopic location, through preferential targets, Grb2-associated binding protein 2 (GAB2) and fibronectin 1 (FN1), and consequent activation of p44/42 mitogen-activated protein kinase (MAPK) and specific matrix metalloproteinases. Treatment with estrogen or epidermal growth factor specifically reduced the expression of mature let-7g through activation of p44/42 MAPK and subsequently stimulated expression of GAB2 and FN1, which, in turn, promoted tumor invasion. We thus identify let-7g as a unique member of the let-7 miRNA family that can serve as a prognostic biomarker in breast cancer and also propose a paradigm used by specific signaling molecules via let-7g to cooperatively promote breast cancer invasion and metastasis. Thus, let-7 family members neither possess equivalent clinicopathologic correlation nor function in breast cancer.