Spatio‐Temporal Parameters of Endosomal Signaling in Cancer: Implications for New Treatment Options

Abstract

The endo/lysosomal system in cells provides membranous platforms to assemble specific signaling complexes and to terminate signal transduction, thus, is essential for physiological signaling. Endocytic organelles can significantly extend signaling of activated cell surface receptors, and may additionally provide distinct locations for the generation of specific signaling outputs. Failures of regulation at different levels of endocytosis, recycling, degradation as well as aberrations in specific endo/lysosomal signaling pathways, such as mTORC1, might lead to different diseases including cancer. Therefore, a better understanding of spatio‐temporal compartmentalization of sub‐cellular signaling might provide an opportunity to interfere with aberrant signal transduction in pathological processes by novel combinatorial therapeutic approaches. J. Cell. Biochem. 117: 836–843, 2016. © 2015 The Authors. Journal of Cellular Biochemistry Published by Wiley Periodicals Inc.

Oncogenic dependence of glioma cells on kish/TMEM167A regulation of vesicular trafficking

“…Vesicle transport plays a central role in cell biology as it provides membranous platforms to assemble specific signaling complexes and to terminate signal transduction (Stasyk & Huber, ). In GB, for example, members of the small GTPases involved in cytoskeletal dynamics and vesicle trafficking, are overexpressed and promote tumor progression (Kim et al, ; Wang & Jiang, ).…”

“…In fact, therapeutic strategies to induce non‐apoptotic cell death in glioma cells rely on endosomal “mis‐trafficking” (Pasupuleti, Grodzki, & Gorin, ). However, inhibitors of the endo/lysosomal system are still far from preclinical development as they target too many common cellular mechanisms with potentially high toxicity at the organism levels (Stasyk & Huber, ).…”

“…Vesicle transport plays a central role in cell biology as it provides membranous platforms to assemble specific signaling complexes and to terminate signal transduction (Stasyk & Huber, 2016).…”

“…However, inhibitors of the endo/lysosomal system are still far from preclinical development as they target too many common cellular mechanisms with potentially high toxicity at the organism levels (Stasyk & Huber, 2016).…”

The INPP4B Tumor Suppressor Modulates EGFR Trafficking and Promotes Triple-Negative Breast Cancer

“…By binding and recruiting effector proteins, phosphoinositides regulate a multitude of cellular functions including endocytosis and intracellular vesicle traffi cking, cytoskeletal remodeling, and signal transduction (20)(21)(22). Importantly, the mechanisms that regulate endocytosis, degradation, or recycling of receptor tyrosine kinases (RTK), including EGFR, MET, and FGFR, profoundly affect the amplitude and duration of signaling output and tumorigenesis (23)(24)(25)(26)(27)(28). PI(3,4)P 2 recruits specific effector proteins such as lamellipodin (29) and TAPP1/2 (30), as well as effectors with more promiscuous phosphoinositide binding such as AKT (31), BAM32 (32), and sorting nexins (33)(34)(35).…”