title: MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis.
abstract: Tumor metastasis involves a series of biological steps during which the tumor cells acquire the ability to invade surrounding tissues and survive outside the original tumor site. During the early stages, the cancer cells undergo an epithelial-mesenchymal transition (EMT). Wnt/β-catenin signaling is known to drive EMT and metastasis. Here we report that Wnt/β-catenin signaling is hyperactivated in metastatic breast cancer cells that express microRNA 374a (miR-374a). In breast cancer cell lines, ectopic overexpression of miR-374a promoted EMT and metastasis both in vitro and in vivo. Furthermore, miR-374a directly targeted and suppressed multiple negative regulators of the Wnt/β-catenin signaling cascade, including WIF1, PTEN, and WNT5A. Notably, miR-374a was markedly upregulated in primary tumor samples from patients with distant metastases and was associated with poor metastasis-free survival. These results demonstrate that miR-374a maintains constitutively activated Wnt/β-catenin signaling and may represent a therapeutic target for early metastatic breast cancer.
authors: Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, Guangdong, China.
authors: Junchao
authors: J
authors: Cai
authors: Hongyu
authors: H
authors: Guan
authors: Lishan
authors: L
authors: Fang
authors: Yi
authors: Y
authors: Yang
authors: Xun
authors: X
authors: Zhu
authors: Jie
authors: J
authors: Yuan
authors: Jueheng
authors: J
authors: Wu
authors: Mengfeng
authors: M
authors: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D014183:Transplantation, Heterologous; D015854:Up-Regulation; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D012097:Repressor Proteins; C485569:WIF1 protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human