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

doi:10.1016/j.stemcr.2017.11.010

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 journal › Article › peer-review

43 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 language	English (US)
Pages (from-to)	212-227
Number of pages	16
Journal	Stem Cell Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1016/j.stemcr.2017.11.010
State	Published - 2018

Keywords

HN1L
LEPR
STAT3
TNBC
cancer stem cells

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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10.1016/j.stemcr.2017.11.010

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Liu, Y., Choi, D. S., Sheng, J., Ensor, J. E., Liang, D. H., 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, M. D., Rosato, R. R., Dave, B., ... Chang, J. C. (2018). HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway. Stem Cell Reports, 10(1), 212-227. https://doi.org/10.1016/j.stemcr.2017.11.010

Liu, Y, Choi, DS, Sheng, J, Ensor, JE, Liang, DH , 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 2018, 'HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway', Stem Cell Reports, vol. 10, no. 1, pp. 212-227. https://doi.org/10.1016/j.stemcr.2017.11.010

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title = "HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway",

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.",

keywords = "HN1L, LEPR, STAT3, TNBC, cancer stem cells",

author = "Yi Liu and Choi, {Dong Soon} and Jianting Sheng and Ensor, {Joe E.} and Liang, {Diana Hwang} and Cristian Rodriguez-Aguayo and Amanda Polley and Steve Benz and Olivier Elemento and Akanksha Verma and Yang Cong and Helen Wong and Wei Qian and Zheng Li and Sergio Granados-Principal and Gabriel Lopez-Berestein and Landis, {Melissa D.} and Rosato, {Roberto R.} and Bhuvanesh Dave and Stephen Wong and Dario Marchetti and Sood, {Anil K.} and Chang, {Jenny C.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2018",

doi = "10.1016/j.stemcr.2017.11.010",

language = "English (US)",

volume = "10",

pages = "212--227",

journal = "Stem Cell Reports",

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T1 - HN1L Promotes Triple-Negative Breast Cancer Stem Cells through LEPR-STAT3 Pathway

AU - Liu, Yi

AU - Choi, Dong Soon

AU - Sheng, Jianting

AU - Ensor, Joe E.

AU - Liang, Diana Hwang

AU - Rodriguez-Aguayo, Cristian

AU - Polley, Amanda

AU - Benz, Steve

AU - Elemento, Olivier

AU - Verma, Akanksha

AU - Cong, Yang

AU - Wong, Helen

AU - Qian, Wei

AU - Li, Zheng

AU - Granados-Principal, Sergio

AU - Lopez-Berestein, Gabriel

AU - Landis, Melissa D.

AU - Rosato, Roberto R.

AU - Dave, Bhuvanesh

AU - Wong, Stephen

AU - Marchetti, Dario

AU - Sood, Anil K.

AU - Chang, Jenny C.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - HN1L

KW - LEPR

KW - STAT3

KW - TNBC

KW - cancer stem cells

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DO - 10.1016/j.stemcr.2017.11.010

M3 - Article

C2 - 29249663

AN - SCOPUS:85039056430

SN - 2213-6711

VL - 10

SP - 212

EP - 227

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 1

ER -

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

Abstract

Keywords

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