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CHDH通过依赖IL17RB/CREB1信号激活促进乳腺癌转移。

CHDH Promotes Breast Cancer Metastasis Relying on IL17RB/CREB1 Signalling Activation.

作者信息

Li Yifei, Liu Yipeng, Yang Xiaowen, Shen Xinzhuang, Liu Zongjun, Ma Yuqiu, Zhan Yiting, Jiang Xinyu, Liang Chengjin, Zhang Xiaoyuan, Liu Huan, Shen Wenzhi

机构信息

Shandong Provincial Precision Medicine Laboratory for Chronic Non-Communicable Diseases, Institute of Precision Medicine, Jining Medical University, Jining, China.

Department of Breast Surgery, Dalian Women and Children's Medical Group, Dalian, China.

出版信息

J Cell Mol Med. 2025 Sep;29(17):e70792. doi: 10.1111/jcmm.70792.

Abstract

The involvement of Choline Dehydrogenase (CHDH) in metabolic disorders and tumour progression has garnered significant scholarly interest. However, the specific role of CHDH in the metastasis and progression of breast cancer (BC) has been less thoroughly investigated. Our research indicates that CHDH protein expression is markedly elevated in breast cancer tissues compared to normal tissues, and this expression is positively correlated with the tumour node metastasis (TNM) stage of breast cancer. Furthermore, CHDH levels were found to be significantly higher in breast cancer cell lines relative to normal breast cells. The silencing of CHDH expression resulted in a reduction of breast cancer cell migration, while the overexpression of CHDH facilitated increased migration and tumour metastasis in vivo. Investigations into the underlying mechanisms revealed that CHDH influences the expression of IL17RB and activates Cyclic-AMP Response Element-Binding Protein (CREB), thereby mediating breast cancer metastasis. The application of an IL17RB antibody and the CREB inhibitor 666-15 effectively abolished CHDH-mediated migration of breast cancer cells in vitro. These findings suggest that CHDH plays a critical role in promoting breast cancer metastasis, potentially offering new targets and strategies for the treatment of metastatic breast cancer.

摘要

胆碱脱氢酶(CHDH)在代谢紊乱和肿瘤进展中的作用已引起学术界的广泛关注。然而,CHDH在乳腺癌(BC)转移和进展中的具体作用尚未得到充分研究。我们的研究表明,与正常组织相比,乳腺癌组织中CHDH蛋白表达显著升高,且这种表达与乳腺癌的肿瘤淋巴结转移(TNM)分期呈正相关。此外,发现乳腺癌细胞系中CHDH水平相对于正常乳腺细胞显著更高。CHDH表达的沉默导致乳腺癌细胞迁移减少,而CHDH的过表达促进了体内迁移增加和肿瘤转移。对潜在机制的研究表明,CHDH影响IL17RB的表达并激活环磷酸腺苷反应元件结合蛋白(CREB),从而介导乳腺癌转移。IL17RB抗体和CREB抑制剂666-15的应用有效地消除了CHDH介导的乳腺癌细胞体外迁移。这些发现表明,CHDH在促进乳腺癌转移中起关键作用,可能为转移性乳腺癌的治疗提供新的靶点和策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4ec/12421421/df1c4b8285ea/JCMM-29-e70792-g007.jpg

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