素通过TGFβ-EGFR轴促进乳腺瘤生长信号传递
Denis Belitškin1, Pauliina Munne1, Shishir M Pant1
1Research Programs Unit/Translational Cancer Medicine Research Program and Medicum, Faculty of Medicine, University of Helsinki, Finland.
Molecular oncology
|October 24, 2023
概括
素蛋白酶,通常在乳腺癌和前列腺癌中发现,通过激活生长途径来驱动瘤生长. 抑制sepsin可以减少瘤扩张和TGFβ/EGFR信号传递,这表明sepsin是治疗点.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 素是一种氨酸蛋白酶,在前列腺癌和乳腺癌中过度表达.
- 赫普辛通过Ras-MAPK通路稳定,并调节细胞外矩阵降解和生长因子通路,如HGF和TGFβ.
- 活性塞塞林促进瘤细胞增殖的确切机制尚不清楚.
研究的目的:
- 调查塞塞林在MYC驱动的乳腺癌生长中的作用.
- 阐明瘤进展中由sepsin调节的下游信号通路.
- 评估sepsin作为癌症治疗的潜在治疗标.
主要方法:
- 在乳腺癌的WAP-Myc小鼠模型中,sepisin基因 (Hpn) 的遗传删除.
- 在初级和转移性部位的瘤生长的分析.
- 评估TGFβ和EGFR信号通路和蛋白质水平.
- 使用中和抗体和小分子抑制剂在3D患者衍生乳腺癌扩展培养物中的抑制研究.
主要成果:
- 遗传删除Hpn显著抑制了原发性和肺转移部位的瘤生长.
- 素的损失导致TGFβ和EGFR信号通路的下调.
- 在sepisin被删除后,EGFR蛋白水平降低了.
- 用抗体或抑制剂向塞西因抑制了TGFβ信号传递和EGFR表达在患者衍生的实验品中.
结论:
- 素作为细胞增殖和瘤生长的调节剂.
- 素通过TGFβ和EGFR信号通路影响瘤的进展.
- 黑代表了TGFβ和EGFR在癌症中的治疗抑制的潜在上游标.
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