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HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway

2017; Elsevier BV; Volume: 10; Issue: 1 Linguagem: Inglês

10.1016/j.stemcr.2017.11.010

2213-6711

Yi Liu, Dong Soon Choi, Jianting Sheng, Joe Ensor, Diana H. Liang, Cristian Rodriguez‐Aguayo, Amanda Polley, Stephen C. Benz, Olivier Elemento, Akanksha Verma, Yang Cong, Helen Wong, Wei Qian, Zheng Li, Sergio Granados‐Principal, Gabriel López-Berestein, Melissa D. Landis, Roberto R. Rosato, Bhuvanesh Dave, Stephen T.C. Wong, Dario Marchetti, Anil K. Sood, Jenny C. Chang,

RNA modifications and cancer

Here, we show that HEMATOLOGICAL AND NEUROLOGICAL EXPRESSED 1-LIKE (HN1L) is a targetable breast cancer stem cell (BCSC) gene that is altered in 25% of whole breast cancer and significantly correlated with shorter overall or relapse-free survival in triple-negative breast cancer (TNBC) patients. HN1L silencing reduced the population of BCSCs, inhibited tumor initiation, resensitized chemoresistant tumors to docetaxel, and hindered cancer progression in multiple TNBC cell line-derived xenografts. Additionally, gene signatures associated with HN1L correlated with shorter disease-free survival of TNBC patients. We defined HN1L as a BCSC transcription regulator for genes involved in the LEPR-STAT3 signaling axis as HN1L binds to a putative consensus upstream sequence of STAT3, LEPTIN RECEPTOR, and MIR-150. Our data reveal that BCSCs in TNBC depend on the transcription regulator HN1L for the sustained activation of the LEPR-STAT3 pathway, which makes it a potentially important target for both prognosis and BCSC therapy.