Serum response factor (SRF) regulates pro-carcinogenic genes in various
cancers, but its role in
oral squamous cell carcinoma (OSCC) remains unclear. SRF expression in 70 OSCC samples was detected via immunohistochemistry. Abundant SRF expressed in OSCC tissues was closely associated with
tumor metastasis. SRF-overexpressing OSCC cells were constructed to evaluate how SRF affects OSCC cell
tumorigenesis and epithelial-to-mesenchymal transition (EMT) in vitro and in vivo. Overexpressed SRF increased OSCC cell migration and invasion in vitro and
tumor growth and invasion in vivo. This promoted EMT, characterized by decreased and increased expression of E- and
N-cadherin, respectively. Furthermore, an analysis of RNA sequences of transcriptional targets of SRF showed that SRF transactivated the indoleamine 2, 3-dioxygenase 1 (IDO1)/
kynurenine-
aryl hydrocarbon receptor (Kyn-AhR) signaling pathway in OSCC cell lines. Direct SRF binding to the IDO1 gene promoter upregulated transcription, which was detected through
chromatin immunoprecipitation and dual
luciferase reporter assays. Inhibiting IDO1 or AhR impaired SRF-induced migration and invasion and prevented EMT in OSCC cells. Our results demonstrated that SRF is a critical regulator of the IDO1/Kyn-AhR signaling pathway. This in turn increases OSCC cell migration and invasion by modulating EMT, which, consequently, favors OSCC cell growth and
metastasis. We revealed a novel molecular mechanism through which SRF modulates OSCC
metastasis. This should provide potential targets or
biomarkers for OSCC diagnosis and treatment.