MACC1 Regulates Clathrin-mediated Endocytosis and Receptor Recycling of Transferrin Receptor and EGFR in Colorectal Cancer

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2021 Jan 20

PMID 33469705

Citations 10

Authors

Francesca Imbastari

Mathias Dahlmann

Anje Sporbert

Camilla Ciolli Mattioli

Tommaso Mari

Florian Scholz

Lena Timm

Shailey Twamley

Rebekka Migotti

Wolfgang Walther

Gunnar Dittmar

Armin Rehm

Ulrike Stein

Affiliations

Soon will be listed here.

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.

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