Format

Send to

Choose Destination
J Mol Cell Biol. 2018 Dec 1;10(6):559-572. doi: 10.1093/jmcb/mjy058.

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

Author information

1
Anhui Key Laboratory for Cellular Dynamics & Chemical Biology, Hefei National Science Center for Physical Sciences at Nanoscale, CAS Center of Excellence in Molecular Cell Sciences, University of Science & Technology of China, Hefei, China.
2
Keck Center for Cellular Dynamics & Department of Physiology, Morehouse School of Medicine, Atlanta, GA, USA.
3
Department of Chemistry, Southern University of Science & Technology, Shenzhen, China.
4
School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, China.
5
Department of Pathology, University of Alabama School of Medicine, Birmingham, AL, USA.

Abstract

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.

PMID:
30395269
PMCID:
PMC6692856
DOI:
10.1093/jmcb/mjy058
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center