The SOX4-Semaphorin3C axis promotes esophageal adenocarcinoma progression

Esophageal adenocarcinoma (EAC) is an aggressive malignancy with an approximately 700 % increase in incidence in Western countries over the past four decades. However, the molecular mechanism driving cancer progression remains elusive. In this study we have identified that SOX4, a transcription factor, is enriched in EACs. SOX4 knockdown or deletion leads to a significant reduction in tumor growth and metastasis. Through integrating RNA-Seq and ChIP-Seq we identified Semaphorin 3C (SEMA3C) as an important downstream target of SOX4. Consistently, knockdown of SEMA3C reduced the growth of EAC cells in vitro and xenografts, accompanied by attenuated epithelial-mesenchymal transition. Our findings identifiy a molecular mechanism through which SOX4 regulates SEMA3C to promote tumor progression, offering potential translational therapeutic target (s) for EAC.