MACC1 regulates clathrin-mediated endocytosis and receptor recycling of transferrin receptor and EGFR in colorectal cancer
Open Access
- 20 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Life Sciences
- Vol. 78 (7), 3525-3542
- https://doi.org/10.1007/s00018-020-03734-1
Abstract
Metastasis Associated in Colon Cancer 1 (MACC1) is a novel prognostic, predictive and causal biomarker for tumor progression and metastasis in many cancer types, including colorectal cancer. Besides its clinical value, little is known about its molecular function. Its similarity to SH3BP4, involved in regulating uptake and recycling of transmembrane receptors, suggests a role of MACC1 in endocytosis. By exploring the MACC1 interactome, we identified the clathrin-mediated endocytosis (CME)-associated proteins CLTC, DNM2 and AP-2 as MACC1 binding partners. We unveiled a MACC1-dependent routing of internalized transferrin receptor towards recycling. Elevated MACC1 expression caused also the activation and internalization of EGFR, a higher rate of receptor recycling, as well as earlier and stronger receptor activation and downstream signaling. These effects are limited by deletion of CME-related protein interaction sites in MACC1. Thus, MACC1 regulates CME and receptor recycling, causing increased growth factor-mediated downstream signaling and cell proliferation. This novel mechanism unveils potential therapeutic intervention points restricting MACC1-driven metastasis.Keywords
Funding Information
- German Cancer Consortium (DKTK, DKTK, DKTK)
- Projekt DEAL
This publication has 53 references indexed in Scilit:
- Rab11-family interacting proteins define spatially and temporally distinct regions within the dynamic Rab11a-dependent recycling systemMolecular Biology of the Cell, 2013
- Transferrin-Mediated Cellular Iron DeliveryCurrent Topics in Membranes, 2012
- Endosome maturationThe EMBO Journal, 2011
- Epidermal growth factor receptors destined for the nucleus are internalized via a clathrin-dependent pathwayBiochemical and Biophysical Research Communications, 2011
- Multi-Image Colocalization and Its Statistical SignificanceBiophysical Journal, 2010
- Pathways and mechanisms of endocytic recyclingNature Reviews Molecular Cell Biology, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantificationNature Biotechnology, 2008
- Clathrin-Mediated Internalization Is Essential for Sustained EGFR Signaling but Dispensable for DegradationDevelopmental Cell, 2008
- Protocol for micro-purification, enrichment, pre-fractionation and storage of peptides for proteomics using StageTipsNature Protocols, 2007