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

Publication date: Available online 14 December 2017 Source:Stem Cell Reports Author(s): Yi Liu, Dong Soon Choi, Jianting Sheng, Joe E. Ensor, Diana Hwang Liang, Cristian Rodriguez-Aguayo, Amanda Polley, Steve Benz, Olivier Elemento, Akanksha Verma, Yang Cong, Helen Wong, Wei Qian, Zheng Li, Sergio Granados-Principal, Gabriel Lopez-Berestein, Melissa D. Landis, Roberto R. Rosato, Bhuvanesh Dave, Stephen Wong, Dario Marchetti, Anil K. Sood, Jenny C. Chang 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 ...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research