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

TitleHN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway.
Publication TypeJournal Article
Year of Publication2018
AuthorsLiu Y, Choi DSoon, Sheng J, Ensor JE, Liang DHwang, Rodriguez-Aguayo C, Polley A, Benz S, Elemento O, Verma A, Cong Y, Wong H, Qian W, Li Z, Granados-Principal S, Lopez-Berestein G, Landis MD, Rosato RR, Dave B, Wong S, Marchetti D, Sood AK, Chang JC
JournalStem Cell Reports
Date Published2018 01 09
KeywordsAnimals, Cell Line, Tumor, Female, Humans, Mice, Mice, SCID, MicroRNAs, Neoplasm Proteins, Neoplastic Stem Cells, Receptors, Leptin, Response Elements, RNA, Neoplasm, Signal Transduction, STAT3 Transcription Factor, Triple Negative Breast Neoplasms

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.

Alternate JournalStem Cell Reports
PubMed ID29249663
PubMed Central IDPMC5768915
Grant ListR01 CA138197 / CA / NCI NIH HHS / United States
U54 CA149196 / CA / NCI NIH HHS / United States