1. LBH is a cancer stem cell- and metastasis-promoting oncogene essential for WNT stem cell function in breast cancer
- Author
-
Bin Wang, Chaitanya Jain, Deukwoo Kwon, Karoline J. Briegel, Zhen Gao, Mahsa Khanlari, Kilan C. Ashad-Bishop, Linsey E Lindley, Steven Xi Chen, Mehrad Nadji, Yuguang Ban, Rehana Qureshi, Sunhwa Hong, Diana J. Azzam, Joyce M. Slingerland, Megan E. Rieger, Koteswararao Garikapati, Andrew H. Sims, and Susan B. Kesmodel
- Subjects
Oncogene ,medicine.medical_treatment ,CD44 ,Wnt signaling pathway ,Stem-cell therapy ,Biology ,medicine.disease ,Metastasis ,Breast cancer ,Cancer stem cell ,medicine ,biology.protein ,Cancer research ,Stem cell - Abstract
Cancer stem cells (CSCs) initiate tumors, resist treatment, and seed lethal metastases; yet CSC-specific treatments are lacking. Aggressive, treatment-resistant triple-negative breast cancers (TNBC) exhibit WNT pathway activation and are CSC enriched. Here, we show that Limb-Bud- and-Heart (LBH), a WNT/β-catenin target required for normal mammary stem cell self-renewal, marks poor prognosis, stem-like TNBC, and is a key controller of breast cancer stemness. LBH is specifically expressed in tumor-initiating CD44+CD24-/low breast CSCs. LBH overexpression confers stem-like, metastatic traits on both TNBC and luminal origin, non-TNBC breast cancer cells by activating stem cell transcriptional programs. Importantly, silencing LBH potently suppresses tumor initiation and metastasis in vivo, and sensitizes TNBC cells to chemotherapy. LBH knockout in the MMTV-Wnt1 breast cancer mouse model, furthermore, revealed LBH is required for WNT-driven breast CSC expansion. Our findings identify LBH as an essential CSC driver downstream of WNT, and a new molecular target for anti-cancer stem cell therapy.
- Published
- 2021
- Full Text
- View/download PDF