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CORO1C，一种新型的 PAK4 结合蛋白，将磷酸化的 PAK4 募集到丝氨酸 99 处的前缘，并促进胃癌细胞的迁移。

CORO1C, a novel PAK4 binding protein, recruits phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2022 May 25;54(5):673-685. doi: 10.3724/abbs.2022044.

DOI:10.3724/abbs.2022044
PMID:35593474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9827817/
Abstract

Gastric cancer is one of the malignant tumors in the world. PAK4 plays an important role in the occurrence and development of gastric cancer, especially in the process of invasion and metastasis. Here we discover that CORO1C, a member of coronin family that regulates microfilament and lamellipodia formation, recruits cytoplasmic PAK4 to the leading edge of gastric cancer cells by C-terminal extension (CE) domain of CORO1C (353-457 aa). The localization of PAK4 on the leading edge of the cell depends on two necessary conditions: the phosphorylation of PAK4 on serine 99 and the binding to the CE domain of CORO1C. Unphosphorylated PAK4 on serine 99 is closely associated with microtubules by PAK4/GEF-H1/Tctex-1 complex. Once phosphorylated, PAK4 is released from microtubule, and then is recruited by CORO1C to the leading edge and regulates the CORO1C/RCC2 (regulator of chromosome condensation 2) complex, leading to the migration of gastric cancer cells. Our results reveal a new mechanism by which PAK4 regulates the migration potential of gastric cancer cells through microtubule-microfilament cross talk.

摘要

胃癌是世界上的恶性肿瘤之一。PAK4 在胃癌的发生和发展中起着重要作用，特别是在侵袭和转移过程中。在这里，我们发现 CORO1C，一种调节微丝和片状伪足形成的 coronin 家族的成员，通过 CORO1C 的 C 端延伸（CE）域（353-457 aa）将细胞质 PAK4 招募到胃癌细胞的前缘。PAK4 在细胞前缘的定位取决于两个必要条件：PAK4 丝氨酸 99 的磷酸化和与 CORO1C 的 CE 域的结合。未磷酸化的 PAK4 丝氨酸 99 通过 PAK4/GEF-H1/Tctex-1 复合物与微管紧密结合。一旦磷酸化，PAK4 就会从微管上释放出来，然后被 CORO1C 招募到前缘，并调节 CORO1C/RCC2（染色体凝聚调节剂 2）复合物，导致胃癌细胞的迁移。我们的结果揭示了 PAK4 通过微管-微丝相互作用调节胃癌细胞迁移潜能的新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/155b6975a92d/ABBS-2021-690-t7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/3e362719c31d/ABBS-2021-690-t1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/904c7199d07f/ABBS-2021-690-t2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/b8f8c94ecf11/ABBS-2021-690-t3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/a887ba68862e/ABBS-2021-690-t4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/a8f62f773d25/ABBS-2021-690-t5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/3b3afb33c6ce/ABBS-2021-690-t6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/155b6975a92d/ABBS-2021-690-t7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/3e362719c31d/ABBS-2021-690-t1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/904c7199d07f/ABBS-2021-690-t2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/b8f8c94ecf11/ABBS-2021-690-t3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/a887ba68862e/ABBS-2021-690-t4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/a8f62f773d25/ABBS-2021-690-t5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/3b3afb33c6ce/ABBS-2021-690-t6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dbf/9827817/155b6975a92d/ABBS-2021-690-t7.jpg

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