High expression of FUSE binding protein 1 in breast cancer stimulates cell proliferation and diminishes drug sensitivity

Abstract

Breast cancer is the most common malignant tumor affecting women worldwide and is divided into the following subtypes: Luminal A, Luminal B, HER-2 overexpression and triple-negative breast cancer (TNBC). TNBC accounts for approximately 15-20% of all breast cancer cases. Due to the characteristics of low differentiation, the likelyhood of recurrence and metastasis, strong invasiveness and the lack of hormone receptors and human epidermal growth factor receptor 2 (HER2), patients with TNBC cannot benefit from endocrine therapy or other available targeted agents. Chemotherapy is one of the main treatments for patients with TNBC, and cisplatin is one of the most commonly used and effective drugs. The human far upstream element binding protein 1 (FBP1) is a potent pro-proliferative and anti-apoptotic oncoprotein, which is overexpressed in numerous tumor types. The present study demonstrated that FBP1 and its target, c-Myc, were more highly expressed in breast cancer tissues compared with para-carcinoma tissues, and the FBP1 and c-Myc levels are decreased by cisplatin treatment. The knockdown of FBP1 in TNBC cells decreased cell proliferation by arresting the cell cycle at the G2 phase. The knockdown of FBP1 decreased the expression of G2 phase-associateed protein cyclin A2, whereas it increased that of cyclin B1 and p-CDC2. Furthermore, the knockdown of FBP1 decreased cell migration and metastasis by downregulating matrix metalloproteinase 2 expression, and enhanced the sensitivity of TNBC cells to cisplatin by inducing apoptosis. These results thus suggest that FBP1 is a potential novel biological marker for the diagnosis and treatment of TNBC.

Evaluating the efficacy and microenvironment changes of HER2 + gastric cancer during HLX02 and Endostar treatment using quantitative MRI

“…However, the prognosis remains poor due to the low targeting ability of chemotherapy and the advanced stage at the time of diagnosis. Human epidermal growth Factor 2 (HER2) is an important factor mediating cell proliferation, differentiation and survival [ 2 ]. It is overexpressed not only in breast cancer but also in gastric cancer [ 3 ].…”

Combination of Immune-Related Network and Molecular Typing Analysis Defines a Three-Gene Signature for Predicting Prognosis of Triple-Negative Breast Cancer

“…The study by Cong et al revealed that aberrant expression of FBP1 in NK cells resulted in their dysfunction by inhibiting glycolysis and impairing viability [ 50 ]. FBP1 knockdown decreased the migration and invasion of MDA-MB-231 cells and enhanced the sensitivity of TNBC cells to cisplatin [ 51 ]. To date, the role of FBP1 in anti-tumor immune response is not well-understood.…”

Development of a novel lipid metabolism-based signature to predict survival and immune response in triple negative breast cancer

“…Among the selected gene signatures, the expression level of CXCL13 has been found linked to the proin ammatory features of macrophages, could predict the response to the combination of chemotherapy with checkpoint inhibitors for TNBCs [39] . FBP1, a gluconeogenesis regulatory enzyme, has been found modulate cell proliferation and chemosensitivity by targeting c-myc in breast cancer [40] . Further mechanism analysis showed that MYC-overexpressing TNBC relied on fatty acid oxidation (FAO), inhibition of FAO may as a potential treatment strategy for MYC-overexpressing TNBC.…”