Stem Cell Reports (Jan 2018)
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 Wong,
- Dario Marchetti,
- Anil K. Sood,
- Jenny C. Chang
Affiliations
- Yi Liu
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Dong Soon Choi
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Jianting Sheng
- Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Houston, TX 77030, USA
- Joe E. Ensor
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Diana Hwang Liang
- Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA
- Cristian Rodriguez-Aguayo
- Center for RNA Interference and Non-Coding RNA, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA
- Amanda Polley
- NantOmics, LLC, Santa Cruz, CA 95060, USA
- Steve Benz
- NantOmics, LLC, Santa Cruz, CA 95060, USA
- Olivier Elemento
- Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA
- Akanksha Verma
- Department of Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10021, USA
- Yang Cong
- Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA
- Helen Wong
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Wei Qian
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Zheng Li
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA
- Sergio Granados-Principal
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Gabriel Lopez-Berestein
- Center for RNA Interference and Non-Coding RNA, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA
- Melissa D. Landis
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Roberto R. Rosato
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Bhuvanesh Dave
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA
- Stephen Wong
- Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Houston, TX 77030, USA
- Dario Marchetti
- Biomarker Research Program, Houston Methodist Research Institute, Houston, TX 77030, USA
- Anil K. Sood
- Center for RNA Interference and Non-Coding RNA, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Experimental Therapeutics, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA
- Jenny C. Chang
- Houston Methodist Cancer Center, Houston Methodist Hospital, 6445 Main Street, Floor 24, Houston, TX 77030, USA; Corresponding author
- DOI
- https://doi.org/10.1016/j.stemcr.2017.11.010
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 212 – 227
Abstract
Summary: 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.
Keywords
