A Noncanonical Role of Fructose-1, 6-Bisphosphatase 1 Is Essential for Inhibition of Notch1 in Breast Cancer

Breast cancer is a leading cause of death in women worldwide, but the underlying mechanisms of breast tumorigenesis remain unclear. Fructose-1, 6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor in breast cancer. However, the mechanisms...

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Bibliographic Details
Published in:Molecular cancer research 2020-05, Vol.18 (5), p.787-796
Main Authors: Lu, Chao, Ren, Chune, Yang, Tingting, Sun, Yonghong, Qiao, Pengyun, Wang, Dan, Lv, Shijun, Yu, Zhenhai
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Proliferation
Female
Fructose-Bisphosphatase - genetics
Fructose-Bisphosphatase - metabolism
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Prognosis
Receptor, Notch1 - antagonists & inhibitors
Survival Rate
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
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Summary:Breast cancer is a leading cause of death in women worldwide, but the underlying mechanisms of breast tumorigenesis remain unclear. Fructose-1, 6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis, was recently shown to be a tumor suppressor in breast cancer. However, the mechanisms of FBP1 as a tumor suppressor in breast cancer remain to be explored. Here we showed that FBP1 bound to Notch1 in breast cancer cells. Moreover, FBP1 enhanced ubiquitination of Notch1, further leading to proteasomal degradation via FBXW7 pathway. In addition, we found that FBP1 significantly repressed the transactivation of Notch1 in breast cancer cells. Functionally, Notch1 was involved in FBP1-mediated tumorigenesis of breast cancer cells and . Totally, these findings indicate that FBP1 inhibits breast tumorigenesis by regulating Notch1 pathway, highlighting FBP1 as a potential therapeutic target for breast cancer. IMPLICATIONS: We demonstrate FBP1 as a novel regulator for Notch1 in breast cancer.
ISSN:1541-7786
1557-3125
DOI:10.1158/1541-7786.MCR-19-0842