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Chromatin-modifying protein 4C (CHMP4C) affects breast cancer cell growth and doxorubicin resistance as a potential breast cancer therapeutic target
The Journal of Antibiotics ( IF 3.3 ) Pub Date : 2023-11-22 , DOI: 10.1038/s41429-023-00683-2
Xiaoyan Jin 1 , Jian Wang 1 , Zhengyi Wang 1 , Wenyang Pang 1 , Yong Chen 1 , Li Yang 2
Affiliation  

Breast cancer (BCa) is one of the common malignancies among women. Doxorubicin (Dox), a type of anthracycline anti-tumor drug, is a first-line chemotherapy drug for BCa. It is badly needed to effectively reverse BCa resistance to Dox and improve the clinical symptoms of BCa. Chromatin Modification protein 4C (CHMP4C) is a subunit of the endosomal sorting complex and is expressed in the nucleus and cytoplasm. CHMP4C has been shown to be overexpressed in multiple types of cancers. However, its possible effects on the progression and drug resistance of BCa are still unclear. In this study, we found CHMP4C was highly expressed in BCa tissues and promoted cell proliferation. In addition, CHMP4C promoted resistance of BCa cells to Dox through targeting Snail. We further found that knockdown of CHMP4C inhibited tumor growth and enhanced sensitivity to Dox in vivo. We therefore thought CHMP4C could serve as a target for decreasing BCa drug resistance.



中文翻译:

染色质修饰蛋白 4C (CHMP4C) 影响乳腺癌细胞生长和阿霉素耐药性,作为潜在的乳腺癌治疗靶点

乳腺癌(BCa)是女性常见的恶性肿瘤之一。阿霉素(Dox)是一种蒽环类抗肿瘤药物,是BCa的一线化疗药物。迫切需要有效逆转BCa对Dox的耐药性并改善BCa的临床症状。染色质修饰蛋白 4C (CHMP4C) 是内体分选复合物的一个亚基,在细胞核和细胞质中表达。CHMP4C 已被证明在多种类型的癌症中过度表达。然而,其对 BCa 进展和耐药性的可能影响仍不清楚。在本研究中,我们发现CHMP4C在BCa组织中高表达并促进细胞增殖。此外,CHMP4C通过靶向Snail促进BCa细胞对Dox的耐药性。我们进一步发现 CHMP4C 的敲低可抑制肿瘤生长并增强体内对 Dox 的敏感性。因此,我们认为 CHMP4C 可以作为降低 BCa 耐药性的靶点。

更新日期:2023-11-22
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