Fatty Acid–Binding Protein 4 (FABP4) Suppresses Proliferation and Migration of Endometrial Cancer Cells via PI3K/Akt Pathway

Abstract

Purpose Endometrial cancer (EC) is the sixth most common cancer in women and its incidence and mortality have been rising over the last decades. The latest research indicates that FABP4 plays a significant role in multiple types of cancer. But few studies were focused on EC. The aim of this article is to investigate whether FABP4 can suppress tumor growth and metastasis of EC via PI3K/Akt pathway to provide a novel therapeutic target for the treatment of EC. Materials and Methods FABP4 mRNA levels of EC were analysed through The Cancer Genome Atlas database (TCGA), and expression of FABP4 in EC cancer tissues was determined by immunohistochemistry (IHC) assays. Stable overexpressing cell lines were established using lentivirus infection to analyze the biological function of FABP4 in vitro. CCK8 assay and colony formation assay were performed to assess cell proliferation ability. Wound healing assay and transwell were performed to analyse migration and invasion of cells. The subcutaneous xenograft mouse model was used to evaluate tumor growth in vivo. Additionally, all protein levels were detected by Western blotting assay. Results We found that the expression of the FABP4 mRNA was decreased in tumor samples compared to normal tissue according to TCGA database analysis. Subsequent experimental mRNA and protein expression analysis confirmed that FABP4 expression was lower in EC tissue than normal endometrial tissue. In addition, we found overexpression of FABP4 inhibited the proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Further functional and mechanistic analysis of FABP4 demonstrated that its function is mediated by restraining the phosphorylation of PI3K/Akt signaling pathway. Conclusion Our studies shed light for the first time about the functional role of FABP4 in EC and provide a novel biomarker for EC as well as a therapeutic target for the therapy of EC.

Diagnostic, Prognostic, and Immunological Roles of FABP4 in Pancancer: A Bioinformatics Analysis

“…Decreased expression of FABP4 was detected in colorectal cancer patients and colorectal cancer cells [ 23 ]. The analysis of mRNA and protein expression in the experiment confirmed that the expression of FABP4 in endometrial cancer tissue was lower than that in normal endometrial tissue [ 24 ]. Nonetheless, the investigators' findings are inconsistent, FABP4 is highly expressed in breast cancer and may play a key role in metastasis and stromal cell interactions [ 8 , 25 ].…”

“…In GO/KEGG analyses, we found indirect roles of FABP4 in the PI3K-Akt signaling pathway, prostate cancer, AMPK, and PPAR signaling pathways. The function of FABP4 is achieved by inhibiting the phosphorylation of the PI3K/Akt signaling pathway [ 24 ]. Exogenous FABP4 activates the PI3K/Akt pathway independent of binding to fatty acids [ 41 ].…”

Comparative Proteomics Analysis Reveals the Reversal Effect of Cryptotanshinone on Gefitinib-Resistant Cells in Epidermal Growth Factor Receptor-Mutant Lung Cancer

“…Fatty acid-binding proteins (FABPs) are a family of highly conserved lipid chaperone molecules with varied functions. One of its members, FABP4, is reported to be overexpressed in cancers, such as prostate and ovarian cancers ( Uehara et al, 2014 ; Gharpure et al, 2018 ), but it is found to suppress cell proliferation in hepatocellular carcinomas and endometrial cancers ( Zhong et al, 2018 ; Wu et al, 2021 ). The role of FABP4 in cancer is still unclear.…”

Role of adipocytokines in endometrial cancer progression

“…On review of the recent studies, other identified adipocytokines, including plasminogen activator inhibitor-1 (PAI-1) ( Wang et al, 2021 ), and fatty acid-binding protein 4 (FABP4) ( Wu et al, 2021 ), also play important roles in regulating various physiological processes. Of note, these adipocytokines have considerable consequences for promoting the proliferation and migration of endometrial cancer cells and may be possible targets for the therapy.…”