SOX4-Semaphorin3C轴促进食管癌进展

IF 10.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-08-26 DOI:10.1016/j.canlet.2025.218005

Tala Fnu , Peiguo Shi , Wanwei Zhang , Yinshan Fang , Yosuke Mitani , Yong Zhang , Joel Gabre , Wael Ei-Rifai , Alexandar Zaika , Qixuan Chen , Jian Zhu , Timothy C. Wang , Ming Jiang , Jianwen Que

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引用次数: 0

摘要

食管腺癌（EAC）是一种侵袭性恶性肿瘤，在过去四十年中，西方国家的发病率增加了约700%。然而，驱动癌症进展的分子机制仍然难以捉摸。在这项研究中，我们发现转录因子SOX4在EACs中富集。SOX4敲低或缺失导致肿瘤生长和转移的显著减少。通过整合RNA-Seq和ChIP-Seq，我们鉴定出信号蛋白3C （SEMA3C）是SOX4重要的下游靶点。与此一致的是，SEMA3C的敲低降低了体外和异种移植物中EAC细胞的生长，并伴有上皮-间质转化的减弱。我们的研究结果确定了SOX4调控SEMA3C促进肿瘤进展的分子机制，为EAC提供了潜在的转化治疗靶点。

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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.

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.