Esophageal squamous cell carcinoma (ESCC), one of the most common malignant tumors, is now afflicting approximately 80% of patients diagnosed with esophageal cancers. The therapeutic effect and prognosis of ESCC remain inadequate due to the unusual early symptoms and rapid malignant progression. SH2 Domain containing 4 A (SH2D4A) is downregulated in malignancies and is closely associated with tumor progression. However, neither the biological functions nor the fundamental mechanisms of SH2D4A on ESCC are known. In this study, it was found that SH2D4A is downregulated in ESCC tissues and cell lines. Incorporating immunohistochemistry and clinicopathological findings, we determined that decreased SH2D4A expression was substantially associated with adverse clinical outcomes. Overexpression of SH2D4A inhibited cell proliferation and migration, whereas suppressing SH2D4A has the opposite effect. SH2D4A mechanistically inhibited cells from proliferating and migrating through the FAK/PI3K/AKT signaling pathway. Furthermore, the results of xenograft tumor growth confirmed the preceding findings. In conclusion, our findings reveal that SH2D4A is a gene which can serve as a cancer suppressor in ESCC and may inhibits the ESCC progression by interfering with the FAK/PI3K/AKT signaling pathway. SH2D4A could act as a target for diagnostic or therapeutic purpose in ESCC.
Keywords: ESCC; FAK /PI3K/AKT signaling pathway; Migration; Proliferation; SH2D4A.
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