β-Catenin Is Required for the Tumorigenic Behavior of Triple-Negative Breast Cancer Cells
Jinhua Xu,Jinhua Xu,Jenifer R. Prosperi,Jenifer R. Prosperi,Noura Choudhury,Olufunmilayo I. Olopade,Kathleen H. Goss +6 more
TLDR
In this paper, 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 small hairpin RNAs (shRNAs).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.read more
Citations
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Journal ArticleDOI
Wnt signaling in cancer.
TL;DR: Current insights into novel components of Wnt pathways are reviewed and how Wnt signaling affects maintenance of cancer stem cells, metastasis and immune control are described.
Journal ArticleDOI
Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer-How We Can Rise to the Challenge.
TL;DR: The evidence presented in this review outlines the role of crucial pathways in TNBC survival following chemotherapy treatment and highlights the importance of using combinatorial drug strategies and incorporating biomarkers in clinical studies.
Journal ArticleDOI
Wnt signaling in triple-negative breast cancer.
Sebastian Öther-Gee Pohl,Naomi Brook,Mark Agostino,Frank Arfuso,Alan Prem Kumar,Arunasalam Dharmarajan +5 more
TL;DR: The complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease are reviewed and regulators of canonical and non-canonical Wnt signaling are summarized.
Journal ArticleDOI
Exon 3 mutations of CTNNB1 drive tumorigenesis: a review.
TL;DR: The current understanding of CTNNB1 mutations, their roles in tumorigenesis and their possible therapeutic implications for cancer are reviewed.
Journal ArticleDOI
WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer
Lorenzo Castagnoli,Valeria Cancila,Sandra L. Cordoba-Romero,Simona Faraci,Giovanna Talarico,Beatrice Belmonte,Marilena V. Iorio,Matteo Milani,Tatiana Volpari,Claudia Chiodoni,Alfredo Hidalgo-Miranda,Elda Tagliabue,Claudio Tripodo,Sabina Sangaletti,Massimo Di Nicola,Serenella M. Pupa +15 more
TL;DR: This study suggests that PD-L1-positive tumor elements with a stemness phenotype may participate in the complex dynamics of TNBC-related immune evasion, which might be targeted through WNT signaling inhibition.
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