Endocytosis and cancer.
Ira Mellman,Yosef Yarden +1 more
TLDR
Mechanisms enabling both major drivers of cancer, p53 and Ras, to bias recycling of integrins and receptor tyrosine kinases (RTKs) are reviewed and pharmacological attempts to harness the peculiar endocytic system of cancer are described.Abstract:
Endocytosis entails selective packaging of cell-surface proteins, such as receptors for cytokines and adhesion components, in cytoplasmic vesicles (endosomes). The series of sorting events that determines the fate of internalized proteins, either degradation in lysosomes or recycling back to the plasma membrane, relies on intrinsic sequence motifs, posttranslational modifications (e.g., phosphorylation and ubiquitination), and transient assemblies of both Rab GTPases and phosphoinositide-binding proteins. This multicomponent process is enhanced and skewed in cancer cells; we review mechanisms enabling both major drivers of cancer, p53 and Ras, to bias recycling of integrins and receptor tyrosine kinases (RTKs). Likewise, cadherins and other junctional proteins of cancer cells are constantly removed from the cell surface, thereby disrupting tissue polarity and instigating motile phenotypes. Mutant forms of RTKs able to evade Cbl-mediated ubiquitination, along with overexpression of the wild-type forms and a variety of defective feedback regulatory loops, are frequently detected in tumors. Finally, we describe pharmacological attempts to harness the peculiar endocytic system of cancer, in favor of effective patient treatment.read more
Citations
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Emerging functions of the EGFR in cancer
TL;DR: The canonical ligand‐induced EGFR signaling pathway is reviewed, with particular emphasis to its regulation by endocytosis and subversion in human tumors, and the most recent advances in uncovering noncanonical EGFR functions in stress‐induced trafficking, autophagy, and energy metabolism are focused on.
Journal ArticleDOI
Endocytic pathways and endosomal trafficking: a primer
TL;DR: This brief overview of endocytic trafficking is written in honor of Renate Fuchs, who retires this year, and describes other sorting machinery and mechanisms, as well as the rab proteins and phosphatidylinositol lipids that serve to dynamically define membrane compartments along the endocytical pathway.
Journal ArticleDOI
An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport
Marlieke L.M. Jongsma,Ilana Berlin,Ruud H. Wijdeven,Lennert Janssen,George M.C. Janssen,Malgorzata A. Garstka,Hans Janssen,Mark Mensink,Peter A. van Veelen,Robbert M. Spaapen,Jacques Neefjes,Jacques Neefjes +11 more
TL;DR: The endoplasmic reticulum (ER)-located ubiquitin ligase Ring finger protein 26 (RNF26) is revealed as the global architect of the entire endosomal system, including the trans-Golgi network (TGN).
Journal ArticleDOI
Signal processing by the endosomal system.
TL;DR: Recent studies reveal a new role of the endosomal network in signal processing that functions analogously to a digital-analogue computer that regulates the specificity and robustness of the signalling response.
Journal ArticleDOI
Critical Functions of the Lysosome in Cancer Biology
TL;DR: This review examines emerging knowledge of how lysosomal processes contribute to the hallmarks of cancer and highlights vulnerabilities that might be exploited for cancer therapy.
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