The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NFκB/HIF-1α activation
Open accessAbstract
High levels of VEGF and leptin are strongly linked to worse prognosis of breast cancer. Leptin signalling up-regulates VEGF in human and mouse mammary tumor cells (MT), but the specific molecular mechanisms are largely unknown. Pharmacologic and genetic approaches were used to dissect the mechanism of leptin regulation of VEGF protein and mRNA in MT (4T1, EMT6 and MMT). A series of VEGF-promoter Luc-reporters (full-length and transcription factor-binding deletions) were transfected into MT to analyze leptin regulation of VEGF transcription. Deletion analysis of VEGF promoter and RNA knockdown shows that HIF-1α and NFκB are essentials for leptin regulation of VEGF. Leptin activation of HIF-1α was mainly linked to canonic (MAPK, PI-3K) and non-canonic (PKC, JNK and p38 MAP) signalling pathways. Leptin non-canonic signalling pathways (JNK, p38 MAP and to less extent PKC) were linked to NFκB activation. SP1 was involved in leptin regulation of VEGF in 4T1 cells. AP1 was not involved and AP2 repressed leptin-induced increase of VEGF. Overall, these data suggest that leptin signalling regulates VEGF mainly through HIF-1α and NFκB. These results delineate a comprehensive mechanism for leptin regulation of VEGF in MT. Disruption of leptin signalling could be used as a novel way to treat breast cancer.
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Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Regulation of hypoxia-inducible factor-1α by NF-κB
van Uden, P., Kenneth, N. S., & Rocha, S. (2008) · Biochemical Journal · doi:10.1042/bj20080476 · Cited by 729
Cited by
Role of Leptin in Inflammation and Vice Versa
Pérez-Pérez, A., Sánchez-Jiménez, F., Vilariño-García, T., & Sánchez-Margalet, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165887 · Cited by 330
Obesity and Breast Cancer: Role of Leptin
Sánchez-Jiménez, F., Pérez-Pérez, A., de la Cruz-Merino, L., & Sánchez-Margalet, V. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00596 · Cited by 268
Volden, P. A., Wonder, E. L., Skor, M. N., Carmean, C. M., Patel, F. N., Ye, H., Kocherginsky, M., McClintock, M. K., Brady, M. J., & Conzen, S. D. (2013) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-12-0458 · Cited by 48
Metadata
- Authors
- Gonzalez-Perez, R. R., Xu, Y., Guo, S., Watters, A., Zhou, W., & Leibovich, S. J.
- Venue
- Cellular Signalling
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 22
- Issue
- 9
- Pages
- 1350-1362
- ISSN
- 0898-6568 (ISSN-L)
- OpenAlex
- W2061390329
- Cited by
- 167
- References
- 3
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
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- Gonzalez-Perez, R. R., Xu, Y., Guo, S., Watters, A., Zhou, W., & Leibovich, S. J. (2010). Leptin upregulates VEGF in breast cancer via canonic and non-canonical signalling pathways and NFκB/HIF-1α activation. Cellular Signalling. https://doi.org/10.1016/j.cellsig.2010.05.003
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