GATA6‑induced FN1 activation promotes the proliferation, invasion and migration of oral squamous cell carcinoma cells

Abstract

GATA binding protein 6 (GATA6) is a transcription factor involved in cell fate decision making and tissue morphogenesis and serves a significant role in the progression of a number of types of cancer. The present study aimed to investigate the role and mechanisms underlying the effects of GATA6 in oral squamous cell carcinoma (OSCC). The expression levels of GATA6 were determined in a number of OSCC cell lines and the expression of GATA6 was knocked down to evaluate its role in the proliferation, invasion and migration of OSCC cells. Subsequently, the association between GATA6 and fibronectin 1 (FN1) was investigated using bioinformatics and further verified using dual-luciferase reporter and chromosomal immunoprecipitation assays. Following the overexpression of FN1 in OSCC cells with GATA6 silencing, functional assays were performed to assess the mechanisms underlying GATA6 in OSCC progression. The results of the present study indicated that OSCC cells exhibited markedly upregulated expression levels of GATA6, while knockdown of GATA6 inhibited the proliferation, colony formation, invasion and migration of OSCC cells. In addition, GATA6 regulated FN1 expression levels by binding to the FN1 promoter. The suppressive effects of GATA6 knockdown on the proliferation, colony formation, invasion and migration of OSCC cells were abolished following FN1 overexpression. In conclusion, the findings of the present study demonstrated that GATA6 promoted the malignant development of OSCC cells by binding to the FN1 promotor. These results may contribute to further understanding the pathogenesis of OSCC and provide potential therapeutic targets for the clinical treatment of OSCC.

LINC00173 blocks GATA6‐mediated transcription of COL5A1 to affect malignant development of oral squamous cell carcinoma

“…29,30 More relevantly, GATA6 has been found to promote the malignant behaviors of OSCC cells by activating the transcription of fibronectin 1. 14 Gain-and loss-of functions studies then revealed that suppression of GATA6 suppressed the malignant behaviors of the OSCC cells, which were rescued by COL5A1 upregulation. The GATA6 upregulation granted the malignant phenotype to OSCC cells; however, the proliferation, migration, invasiveness, apoptosis resistance, tumorigenesis and pro-angiogenic activity of the cells were blocked by further LINC00173 overexpression.…”

“…13 GATA6 has been found to promote the malignant behaviors of OSCC cells by activating transcription of fibronectin 1. 14 Therefore, we postulated that there might be a GATA6-COL5A1 in OSCC as well that drives the malignant progression, and LINC00173 may influence the interaction and thus affect the malignant properties of cancer cells.…”

“…As a member of the GATA family of zinc‐finger TFs, GATA6 participates in cell lineage differentiation and organogenesis of many tissue types and is linked to tumor development 13 . GATA6 has been found to promote the malignant behaviors of OSCC cells by activating transcription of fibronectin 1 14 . Therefore, we postulated that there might be a GATA6‐COL5A1 in OSCC as well that drives the malignant progression, and LINC00173 may influence the interaction and thus affect the malignant properties of cancer cells.…”

Pathogenesis and prognosis of primary oral squamous cell carcinoma based on microRNAs target genes: a systems biology approach

“…GATA6 upregulation has been shown in several tumors in the past, including CRC [ 65 ], gastric cancer [ 66 ], and cholangiocarcinoma [ 67 ]. According to Zhai and Luo [ 8 ], OSCC cell lines (HN4, HN6, SCC9, and Cal27) overexpress GATA6 in comparison to human normal oral mucosal epithelial keratinocytes. Furthermore, GATA6 knockdown suppressed the colony formation, proliferation, migration, and invasion of cancerous cells.…”

“…This is because many OSCC patients are often diagnosed in advanced stages. OSCC has remained one of the mortal malignancies worldwide, with a 5-year survival rate of approximately 50%, indicating that the prognosis of OSCC patients is poor [7][8][9][10][11][12]. Thus, illustrating the exact mechanisms and markers underlying the development of OSCC may elevate patient survival [8,10].…”