PKCε-mediated c-Met endosomal processing directs fluctuant c-Met-JNK-paxillin signaling for tumor progression of HepG2

Cellular Signalling
Chi-Tan HuWen-Sheng Wu

Abstract

Hepatocyte growth factor (HGF) induced c-Met signaling play critical roles in the progression of hepatocellular carcinoma (HCC). However, c-Met targeting approaches suffered resistance and side effect, thus identification of more suitable downstream targets is needed. Recently, we demonstrated HGF-induced fluctuant ERK/paxillin signaling within 24h. We further examined the underlying mechanisms for fluctuant c-Met/JNK/paxillin signal cascade within 12h. HGF-induced phosphorylation of c-Met, JNK, and paxillin (Ser178) shared a common fluctuation pattern characterized by an initial peak at 0.5h, a middle drop at 4h, and a later peak at 10h. Dynasore, the inhibitor of dynamin, suppressed HGF-induced c-Met internalization and phosphorylation of JNK and paxillin (Ser178) at 0.5h, indicating that endosome formation is required for initial signal enhancement. Further, depletion of PKCε not only enhanced HGF-induced phosphorylation of JNK and paxillin (Ser178) but also prevented c-Met degradation at 0.5h, suggesting that PKCε mediated c-Met degradation for signal declination. On the other hand, HGF induced colocalizations of both phosphorylated JNK and paxillin with the endosomal recycling protein GGA3 at 10h and depletion of GGA3 abol...Continue Reading

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Citations

Feb 26, 2016·Carcinogenesis·Jack Zhang, Andy Babic
Nov 1, 2015·Biochemical and Biophysical Research Communications·Hideaki UenoKentaro Mori
Oct 28, 2015·Journal of Cellular Biochemistry·Taras Stasyk, Lukas A Huber
Jul 7, 2020·Frontiers in Cell and Developmental Biology·Xinyue HuXing Yu
Apr 20, 2018·Journal of Cellular Physiology·Keywan Mortezaee
Feb 20, 2017·Journal of Hematology & Oncology·Ana María López-ColoméEdith López
Mar 3, 2020·Frontiers in Cell and Developmental Biology·Haiyu WangZujiang Yu
Jul 23, 2021·Life Science Alliance·Frank JühlingThomas F Baumert

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