癌症相关纤维细胞的细胞外矩阵产生子集通过SRC激活和G0S2上调驱动乳腺癌中的化学抵抗
Isabella Hofer1, Yann Kieffer2, Arianna Mencattini3
1Institut Curie, Paris, France.
Cancer research
|November 12, 2025
概括
特定的与癌症相关的纤维细胞群在三阴性乳腺癌 (TNBC) 中驱动化疗耐药性. 细胞外基质产生肌纤维细胞 (ECM-myCAFs) 激活SRC激酶并上调G0S2,在治疗期间促进TNBC细胞存活.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 细胞和分子医学 细胞和分子医学
背景情况:
- 化疗耐药性是治疗三阴性乳腺癌 (TNBC) 的重大挑战.
- 癌症相关纤维细胞 (CAF) 影响治疗反应,但特定的CAF亚型驱动化学抵抗需要阐明.
研究的目的:
- 为了识别和描述不同的CAF种群,这些种群有助于TNBC的化疗耐药性.
- 阐明特定CAFs调解化电阻的分子机制.
主要方法:
- 从TNBC队列中分析患者数据.
- 外体瘤芯片 (ToC) 建模.
- 单细胞RNA测序,先进的细胞成像和功能测试.
主要成果:
- 一个特定的CAF群体,细胞外矩阵产生肌纤维细胞 (ECM-myCAFs),被确定为介导化学抵抗.
- 化疗敏感患者的ECM-myCAF比率下降,但在化疗后的化疗耐药患者保持不变.
- 在TNBC细胞中,ECM-myCAFs通过SRC激酶激活和G0S2上调促进了TNBC细胞的存活.
结论:
- 在TNBC中,ECM-myCAF在调解化疗耐药性方面发挥着独特的作用.
- G0S2被确定为由ECM-myCAFs驱动的化学抵抗的关键调解者.
- 向SRC激酶或G0S2可以克服TNBC中ECM-myCAF诱导的化学抵抗.
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