title: LGR5 Promotes Breast Cancer Progression and Maintains Stem-Like Cells Through Activation of Wnt/β-Catenin Signaling.
abstract: The cancer stem cell (CSC) hypothesis suggests that a subset of cancer cells possesses stem cell properties and is crucial in tumor initiation, metastasis, and drug resistance. To determine the mechanism of CSCs in breast cancer, we focused on LGR5, a marker of adult stem cells that potentially serves as a functional factor in CSCs. LGR5 overexpression was detected in breast cancer and significantly associated with breast cancer recurrence and poor outcome. LGR5 promoted cell mobility, tumor formation, and epithelial-mesenchymal transition in breast cancer cells by activating Wnt/β-catenin signaling. In addition, LGR5 was more highly expressed in tumorspheres and increased the stemness of breast cancer cells. Compared with LGR5 low-expression (LGR5(low) ) cells, LGR5(high) cells exhibited CSC/tumor-initiating cell-like properties, including the formation of self-renewing spheres and high tumorigenicity. Importantly, our studies indicate that LGR5 activation of Wnt/β-catenin signaling is a possible mechanism to regulate breast CSC/tumor-initiating cell renewal. These findings indicate that LGR5 not only participates in carcinogenesis but also maintained stemness by activating Wnt/β-catenin signaling in breast cancer.
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Hailin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xie
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Cailu
authors.initials: C
authors.lastname: Song
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
authors.forename: Neng
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Breast Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008875:Middle Aged; D014411:Neoplastic Stem Cells; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D018874:Spheroids, Cellular / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics*
chemical_list: C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; D051176:beta Catenin
keywords: Breast cancer; Cancer stem cell; EMT; LGR5; Wnt/β-Catenin