Leptin Signaling Affects Survival and Chemoresistance of Estrogen Receptor Negative Breast Cancer
Estrogen-receptor-negative breast cancer (BCER-) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER- progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER- patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER- patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER- patients. Targeting OBR signaling could improve chemotherapeutic efficacy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
International journal of molecular sciences - 21(2020), 11 vom: 27. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lipsey, Crystal C [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.02.2021 Date Revised 03.11.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms21113794 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310516846 |
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| 245 | 1 | 0 | |a Leptin Signaling Affects Survival and Chemoresistance of Estrogen Receptor Negative Breast Cancer |
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| 520 | |a Estrogen-receptor-negative breast cancer (BCER-) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER- progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER- patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER- patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER- patients. Targeting OBR signaling could improve chemotherapeutic efficacy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a chemoresistance | |
| 650 | 4 | |a estrogen receptor negative breast cancer survival | |
| 650 | 4 | |a leptin | |
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| 650 | 4 | |a obesity-related cancer | |
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| 700 | 1 | |a Harbuzariu, Adriana |e verfasserin |4 aut | |
| 700 | 1 | |a Robey, Robert W |e verfasserin |4 aut | |
| 700 | 1 | |a Huff, Lyn M |e verfasserin |4 aut | |
| 700 | 1 | |a Gottesman, Michael M |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez-Perez, Ruben R |e verfasserin |4 aut | |
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