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MACC1 regulates clathrin-mediated endocytosis and receptor recycling of transferrin receptor and EGFR in colorectal cancer

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Item Type:Article
Title:MACC1 regulates clathrin-mediated endocytosis and receptor recycling of transferrin receptor and EGFR in colorectal cancer
Creators Name:Imbastari, F. and Dahlmann, M. and Sporbert, A. and Mattioli, C.C. and Mari, T. and Scholz, F. and Timm, L. and Twamley, S. and Migotti, R. and Walther, W. and Dittmar, G. and Rehm, A. and Stein, U.
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:CME, Receptor Recycling, MACC1, Transferrin Receptor, EGFR, Colorectal Cancer, Animals, Mice
Source:Cellular and Molecular Life Sciences
ISSN:1420-682X
Publisher:Springer
Date:20 January 2021
Official Publication:https://doi.org/10.1007/s00018-020-03734-1
PubMed:View item in PubMed

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