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

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

Stem cell reports (2017-12-19)
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
PMID29249663
ABSTRACT

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.