title: β-Catenin is required for the tumorigenic behavior of triple-negative breast cancer cells.
abstract: Our previous data illustrated that activation of the canonical Wnt signaling pathway was enriched in triple-negative breast cancer and associated with reduced overall survival in all patients. To determine whether Wnt signaling may be a promising therapeutic target for triple-negative breast cancer, we investigated whether β-catenin was necessary for tumorigenic behaviors in vivo and in vitro. β-catenin expression level was significantly reduced in two human triple-negative breast cancer cell lines, MDA-MB-231 and HCC38, using lentiviral delivery of β-catenin-specific small hairpin RNAs (shRNAs). Upon implantation of the cells in the mammary fat pad of immunocompromised mice, we found that β-catenin shRNA HCC38 cells formed markedly smaller tumors than control cells and grew much more slowly. In in vitro assays, β-catenin silencing significantly reduced the percentage of Aldefluor-positive cells, a read-out of the stem-like cell population, as well as the expression of stem cell-related target genes including Bmi-1 and c-Myc. β-catenin-knockdown cells were also significantly impaired in their ability to migrate in wound-filling assays and form anchorage-independent colonies in soft agar. β-catenin-knockdown cells were more sensitive to chemotherapeutic agents doxorubicin and cisplatin. Collectively, these data suggest that β-catenin is required for triple-negative breast cancer development by controlling numerous tumor-associated properties, such as migration, stemness, anchorage-independent growth and chemosensitivity.
authors: Department of Surgery and Comprehensive Cancer Center, University of Chicago, Chicago, IL 60637, United States of America; Department of Medicine, University of Chicago, Chicago, IL 60637, United States of America; School of Medicine, Jianghan University, Wuhan, Hubei 430056, P.R. China.
authors: Jinhua
authors: J
authors: Xu
authors: Department of Surgery and Comprehensive Cancer Center, University of Chicago, Chicago, IL 60637, United States of America; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, IN 46530, United States of America.
authors: Jenifer R
authors: JR
authors: Prosperi
authors: Department of Surgery and Comprehensive Cancer Center, University of Chicago, Chicago, IL 60637, United States of America.
authors: Noura
authors: N
authors: Choudhury
authors: Department of Medicine, University of Chicago, Chicago, IL 60637, United States of America.
authors: Olufunmilayo I
authors: OI
authors: Olopade
authors: Department of Surgery and Comprehensive Cancer Center, University of Chicago, Chicago, IL 60637, United States of America.
authors: Kathleen H
authors: KH
authors: Goss
mesh_terms: D000818:Animals; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051176:beta Catenin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D051176:beta Catenin