title: Pivotal role of reduced let-7g expression in breast cancer invasion and metastasis.
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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, PR China.
authors.forename: Pengxu
authors.initials: P
authors.lastname: Qian
authors.forename: Zehua
authors.initials: Z
authors.lastname: Zuo
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Wu
authors.forename: Xianyi
authors.initials: X
authors.lastname: Meng
authors.forename: Gaopeng
authors.initials: G
authors.lastname: Li
authors.forename: Zhengzhou
authors.initials: Z
authors.lastname: Wu
authors.forename: Weijie
authors.initials: W
authors.lastname: Zhang
authors.forename: Sheng
authors.initials: S
authors.lastname: Tan
authors.forename: Vijay
authors.initials: V
authors.lastname: Pandey
authors.forename: Yandan
authors.initials: Y
authors.lastname: Yao
authors.forename: Puyue
authors.initials: P
authors.lastname: Wang
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Erwei
authors.initials: E
authors.lastname: Song
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.forename: Tao
authors.initials: T
authors.lastname: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D002277:Carcinoma / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D020782:Matrix Metalloproteinases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004967:Estrogens; C067625:FN1 protein, human; D005353:Fibronectins; C490895:GAB2 protein, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D004815:Epidermal Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020782:Matrix Metalloproteinases