Acetylation of ACAP4 regulates CCL18-elicited breast cancer cell migration and invasion

Tumor metastasis represents the main causes of cancer-related death. Our recent study showed that chemokine CCL18 secreted from tumor-associated macrophages regulates breast tumor metastasis, but the underlying mechanisms remain less clear. Here, we show that ARF6 GTPase-activating protein ACAP4 reg...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular cell biology 2018-12, Vol.10 (6), p.559-572
Main Authors: Song, Xiaoyu, Liu, Wei, Yuan, Xiao, Jiang, Jiying, Wang, Wanjuan, Mullen, McKay, Zhao, Xuannv, Zhang, Yin, Liu, Fusheng, Du, Shihao, Rehman, Adeel, Tian, Ruijun, Li, Jian, Frost, Andra, Song, Zhenwei, Green, Hadiyah-Nicole, Henry, Calmour, Liu, Xing, Ding, Xia, Wang, Dongmei, Yao, Xuebiao
Format: Article
Language:English
Subjects:
Acetylation
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Line
Cell Line, Tumor
Cell Movement
Chemokines, CC - metabolism
Female
GTPase-Activating Proteins - metabolism
Humans
Neoplasm Invasiveness - pathology
Original
p300-CBP Transcription Factors - metabolism
Protein Interaction Maps
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tumor metastasis represents the main causes of cancer-related death. Our recent study showed that chemokine CCL18 secreted from tumor-associated macrophages regulates breast tumor metastasis, but the underlying mechanisms remain less clear. Here, we show that ARF6 GTPase-activating protein ACAP4 regulates CCL18-elicited breast cancer cell migration via the acetyltransferase PCAF-mediated acetylation. CCL18 stimulation elicited breast cancer cell migration and invasion via PCAF-dependent acetylation. ACAP4 physically interacts with PCAF and is a cognate substrate of PCAF during CCL18 stimulation. The acetylation site of ACAP4 by PCAF was mapped to Lys311 by mass spectrometric analyses. Importantly, dynamic acetylation of ACAP4 is essential for CCL18-induced breast cancer cell migration and invasion, as overexpression of the persistent acetylation-mimicking or non-acetylatable ACAP4 mutant blocked CCL18-elicited cell migration and invasion. Mechanistically, the acetylation of ACAP4 at Lys311 reduced the lipid-binding activity of ACAP4 to ensure a robust and dynamic cycling of ARF6-ACAP4 complex with plasma membrane in response to CCL18 stimulation. Thus, these results present a previously undefined mechanism by which CCL18-elicited acetylation of the PH domain controls dynamic interaction between ACAP4 and plasma membrane during breast cancer cell migration and invasion.
ISSN:1759-4685
1674-2788
1759-4685
DOI:10.1093/jmcb/mjy058