Department of Surgical Oncology, Taizhou Municipal Hospital, Taizhou, Zhejiang, 318000, China.
Department of Anesthesiology, Taizhou Municipal Hospital, Taizhou, Zhejiang, 318000, China.
J Antibiot (Tokyo). 2024 Feb;77(2):93-101. doi: 10.1038/s41429-023-00683-2. Epub 2023 Nov 22.
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.
乳腺癌（BCa）是女性常见的恶性肿瘤之一。多柔比星（Dox）是一种蒽环类抗肿瘤药物，是 BCa 的一线化疗药物。有效逆转 BCa 对 Dox 的耐药性并改善 BCa 的临床症状，这是非常需要的。染色质修饰蛋白 4C（CHMP4C）是内体分选复合物的亚基，在细胞核和细胞质中表达。已经表明 CHMP4C 在多种类型的癌症中过表达。然而，其对 BCa 进展和耐药性的可能影响尚不清楚。在这项研究中，我们发现 CHMP4C 在 BCa 组织中高度表达，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，敲低 CHMP4C 抑制体内肿瘤生长并增强对 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。
