Expression of SIX1 and TEAD1 in colorectal cancer and their synergistic effect on tumor growth via CTGF expression

Abstract

The transcription factors SIX1 and TEAD1 are implicated in various malignancies, but their expression patterns and potential interplay in colorectal cancer (CRC) remain incompletely understood. Immunohistochemistry was performed to detect SIX1, TEAD1, and CTGF expression in CRC and hyperplastic polyp tissues. A subcutaneous xenograft model was established using HCT116 cells with stable knockdown of SIX1 and/or TEAD1. Tumor growth was monitored, and xenograft tissues were analyzed by Western blot, qPCR, and immunohistochemistry. Bioinformatics analysis was performed using TCGA database. Dual-luciferase reporter assays and ChIP-qPCR were conducted to investigate direct binding to the CTGF promoter. SIX1, TEAD1, and CTGF were significantly upregulated in CRC tissues compared to controls. Combined knockdown of SIX1 and TEAD1 synergistically inhibited tumor growth and suppressed CTGF expression at both protein and mRNA levels. Bliss independence analysis confirmed synergy. TCGA analysis confirmed significant differential expression of these genes and positive correlations among them. Dual-luciferase and ChIP-qPCR demonstrated direct binding of SIX1 and TEAD1 to the CTGF promoter. SIX1 and TEAD1 are highly expressed in CRC and synergistically promote tumor growth through convergent regulation of CTGF. Combined targeting of these transcription factors may represent a potential therapeutic strategy for CRC.