CORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells

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 f...

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Main Authors: Li Xiaodong, Chen Min, Yuan Ying, Li Jiabin, Li Feng
Format: Article
Language:English
Published: China Science Publishing & Media Ltd. 2022-05-01
Series:Acta Biochimica et Biophysica Sinica
Subjects:
Online Access:https://www.sciengine.com/doi/10.3724/abbs.2022044
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author Li Xiaodong
Chen Min
Yuan Ying
Li Jiabin
Li Feng
author_facet Li Xiaodong
Chen Min
Yuan Ying
Li Jiabin
Li Feng
author_sort Li Xiaodong
collection DOAJ
description 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 <sc>(353–457 aa).</sc> 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.
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spelling doaj.art-f0cbf1e231044da8912f28d4ced23eec2023-11-07T00:58:04ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-05-015467368510.3724/abbs.202204420d259ccCORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cellsLi Xiaodong0Chen Min1Yuan Ying2Li Jiabin3Li Feng4[][][][][]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 <sc>(353–457 aa).</sc> 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.https://www.sciengine.com/doi/10.3724/abbs.2022044PAK4CORO1CRCC2microtubulemigrationgastric cancer cell
spellingShingle Li Xiaodong
Chen Min
Yuan Ying
Li Jiabin
Li Feng
CORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells
Acta Biochimica et Biophysica Sinica
PAK4
CORO1C
RCC2
microtubule
migration
gastric cancer cell
title CORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells
title_full CORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells
title_fullStr CORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells
title_full_unstemmed CORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells
title_short CORO1C, a novel PAK4 binding protein, recruits<?A3B2 ACK?>phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells
title_sort coro1c a novel pak4 binding protein recruits a3b2 ack phospho pak4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells
topic PAK4
CORO1C
RCC2
microtubule
migration
gastric cancer cell
url https://www.sciengine.com/doi/10.3724/abbs.2022044
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