FAST1 Predicts Poor Survival of Renal Carcinoma and Promotes Its Progression Through the TGF-β/Smad Pathway

Abstract

Purpose Renal carcinoma (RC) originates in the renal tubular epithelial system, among which renal cell carcinoma (RCC) is the most frequent one. The forkhead activin signal transducer 1 (FAST1) has been shown to interfere with tumor progression as an oncogene, while its role in RC is limited. Therefore, this paper explored the prognostic significance, specific effects, and related mechanisms of FAST1 on RC. Patients and Methods Cell colony formation assay, cell counting kit-8 (CCK8) assay, flow cytometry and Transwell assay were used to test cell proliferation, viability, apoptosis, migration and invasion, respectively. Western blot (WB) was employed to determine the protein level of FAST1. Results Our study confirmed that FAST1 was up-regulated in RC tissues and cell lines, and its overexpression often represented a poor prognosis of RC patients. Meanwhile, the in vitro experiments showed that overexpressing FAST1 facilitated RC cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and repressed cell apoptosis. In addition, the in vivo experiments illustrated that the up-regulation of FAST1 strengthened tumor growth. On the contrary, knocking down FAST1 had the opposite effects. Mechanistically, The TGF-β/Smad pathway contributed to RC evolvement and was activated by FAST1 both in vitro and in vivo. Conclusion This article suggests that FAST1 exerts a carcinogenic role in RC by regulating the TGF-β/Smad signaling.

Inflammatory Networks in Renal Cell Carcinoma

“…Integrin signaling potentiated TGFβ1-induced E-cadherin depletion in vitro, mediated by the EMT-associated transcription factor Snai1 [ 298 ]. Forkhead activin signal transducer 1 (FAST1, FOXH1) is upregulated in RCC and mediates activation of the TGFβ/Smad signaling pathway, leading to increased cell viability, proliferation, migration, invasion, EMT, and reduced apoptosis as well as increased tumor growth [ 299 ]. Neutralizing TGFβ in a heterotopic cancer model decreased the size of tumors and inhibited vascularization [ 300 ].…”