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首页> 外文期刊>European Journal of Cell Biology: Journal of Deutsche Gesellschaft fur Elektronenmikroskopie: Journal of Deutsche Gesellschaft fur Zellbiologie >Native type IV collagen induces cell migration through a CD9 and DDR1-dependent pathway in MDA-MB-231 breast cancer cells
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Native type IV collagen induces cell migration through a CD9 and DDR1-dependent pathway in MDA-MB-231 breast cancer cells

机译:天然IV型胶原通过MDA-MB-231乳腺癌细胞中的CD9和DDR1依赖性途径诱导细胞迁移

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摘要

CD9 is a member of the tetraspanin family and is widely expressed in the plasma membrane of several cell types as well as malignant cells. CD9 associates with a number of transmembrane proteins, which facilitates biological processes, including cell signaling, adhesion, migration and proliferation. DDR1 is activated by native type IV collagen and overexpressed in human breast cancer. Type IV collagen is the main component of basement membranes, and may interact with cell surface biomolecules, promoting adhesion and motility. However, the role of DDR1 and type IV collagen in the regulation of CD9-cell surface levels and migration in breast cancer cells has not been studied in detail. We demonstrate here that native type IV collagen induces a transient increase of CD9-cell surface levels through a DDR1-dependent pathway in MDA-MB-231 breast cancer cells, as revealed by flow cytometry and Western blotting using specific antibodies that recognize CD9. In contrast, type IV collagen does not induce any increase of CD9-cell surface levels in the mammary non-tumorigenic epithelial cells MCF10A and MCF12A. Transient increase of CD9-cell surface levels is coupled with clathrin-mediated endocytosis and it is dependent of DDR1 expression. In addition, type IV collagen induces cell migration through a DDR1 and CD9-dependent pathway. In summary, our data demonstrate, for the first time, that native type IV collagen induces a transient increase of CD9-cell surface levels and cell migration through a DDR1 and CD9-dependent pathway in MDA-MB-231 breast cancer cells
机译:CD9是四跨膜蛋白家族的成员,并且在几种细胞类型以及恶性细胞的质膜中广泛表达。 CD9与许多跨膜蛋白缔合,从而促进了生物过程,包括细胞信号传导,粘附,迁移和增殖。 DDR1被天然IV型胶原激活,并在人类乳腺癌中过表达。 IV型胶原蛋白是基底膜的主要成分,并可能与细胞表面生物分子相互作用,从而促进粘附和运动。然而,尚未详细研究DDR1和IV型胶原在乳腺癌细胞中调节CD9细胞表面水平和迁移中的作用。我们在这里证明,天然IV型胶原蛋白通过MDA-MB-231乳腺癌细胞中的DDR1依赖性途径诱导CD9细胞表面水平的瞬时增加,这是通过流式细胞仪和使用识别CD9的特异性抗体进行的蛋白质印迹揭示的。相比之下,IV型胶原不会在乳腺非致瘤性上皮细胞MCF10A和MCF12A中诱导CD9细胞表面水平的任何增加。 CD9细胞表面水平的瞬时增加与网格蛋白介导的胞吞作用有关,它依赖于DDR1表达。此外,IV型胶原蛋白通过DDR1和CD9依赖性途径诱导细胞迁移。总而言之,我们的数据首次证明了天然IV型胶原蛋白通过MDA-MB-231乳腺癌细胞中的DDR1和CD9依赖性途径诱导CD9细胞表面水平的瞬时增加和细胞迁移

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