Bioinformatic Analyses and Experimental Verification Reveal that High FSTL3 Expression Promotes EMT via Fibronectin-1/α5β1 Interaction in Colorectal Cancer

Abstract

Background: Colorectal cancer (CRC) is a typical cancer prevalent worldwide. Despite the conventional treatments, CRC has a poor prognosis due to relapse and metastasis. Moreover, there is a dearth of sensitive biomarkers for predicting prognosis in CRC.Methods: This study used a bioinformatics approach combining validation experiments to examine the value of follistatin-like 3 (FSTL3) as a prognostic predictor and therapeutic target in CRC.Results:FSTL3 was remarkably upregulated in the CRC samples. FSTL3 overexpression was significantly associated with a poor prognosis. FSTL3 was found to activate the epithelial-mesenchymal transition by promoting the binding of FN1 to α5β1. FSTL3 expression was also positively correlated with the abundance of the potent immunosuppressors, M2 macrophages.Conclusion:FSTL3 overexpression affects CRC prognosis and thus, FSTL3 can be a prognostic biomarker and therapeutic target with potential applications in CRC.

The cytoplasmic expression of FSTL3 correlates with colorectal cancer progression, metastasis status and prognosis

“…The data we analysed are consistent with previous research on related topics 27–29 . Our previous analyses of FSTL1 in lung cancer have shown that its location within the cell may have a significant effect on its function 30,31 .…”

“…FSTL3 is involved in macrophage infiltration 27 . In particular, FSTL3 levels have been correlated with M2 macrophages.…”

“…FSTL3 is involved in macrophage infiltration. 27 In particular, FSTL3 levels have been correlated with M2 macrophages. FSTL3 overexpression results in an increase in macrophage-associated markers, such as CD206 and CD163.…”

“…The data we analysed are consistent with previous research on related topics. [27][28][29] Our previous analyses of FSTL1 in lung cancer have shown that its location within the cell may have a significant effect on its function. 30,31 Thus, in this study, we sought to determine whether the distribution of FSTL3 in tissues is associated with different clinical significance.…”

Role of pericytes in the development of cerebral cavernous malformations

“…Fibronectin also induces epithelial-mesenchymal transition (EMT), 48 , 49 , 50 and intervention of fibronectin attenuates EMT. 48 , 51 EMT is closely related to endothelial-to-mesenchymal transition (EndMT) with highly similar mechanisms.…”