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

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 WongDario Marchetti, Anil K. Sood, Jenny C. Chang

Research output: Contribution to journalArticle

23 Scopus citations

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. Yi et al. describe HN1L as a novel transcription regulator for breast cancer stem cells (BCSCs) in triple-negative breast cancer (TNBC), promoting LEPR and miR-150 expression and activating the STAT3 pathway. Since BCSCs contribute to chemoresistance and metastasis in TNBC, further investigation of HN1L will offer new therapeutic strategies.

Original languageEnglish (US)
JournalStem Cell Reports
Early online dateDec 8 2017
DOIs
StateE-pub ahead of print - Dec 8 2017

Keywords

  • Cancer stem cells
  • HN1L
  • LEPR
  • STAT3
  • TNBC

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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