HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway. Academic Article uri icon

Overview

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.

publication date

  • December 14, 2017

Research

keywords

  • Neoplasm Proteins
  • Neoplastic Stem Cells
  • Receptors, Leptin
  • STAT3 Transcription Factor
  • Signal Transduction
  • Triple Negative Breast Neoplasms

Identity

PubMed Central ID

  • PMC5768915

Scopus Document Identifier

  • 85039056430

Digital Object Identifier (DOI)

  • 10.1016/j.stemcr.2017.11.010

PubMed ID

  • 29249663

Additional Document Info

volume

  • 10

issue

  • 1