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LBH is a cancer stem cell- and metastasis-driving oncogene essential for WNT stem cell function in breast cancer

Garikapati, K.; Ashad-Bishop, K.; Hong, S.; Qureshi, R.; Rieger, M. E.; Lindley, L. E.; Wang, B.; Azzam, D. J.; Khanlari, M.; Nadji, M.; Jain, C.; Kwon, D.; Ban, Y.; Gao, Z.; Chen, S. X.; Sims, A. H.; Kesmodel, S. B.; Slingerland, J. M.; Briegel, K. J.

2021-01-30 cancer biology
10.1101/2021.01.29.428659 bioRxiv
Show 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/{beta}-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.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.