PAK4 kinase-mediated SCG10 phosphorylation involved in gastric cancer metastasis.

Abstract:

:Superior cervical ganglia 10 (SCG10), as a microtubule (MT) destabilizer, maintains MT homeostasis and has a critical role in neuronal development, but its function in tumorigenesis has not been characterized. In the present study, we demonstrated that p21-activated kinase 4 (PAK4)-mediated SCG10 phosphorylation regulates MT homeostasis in metastatic gastric cancer. Our results indicate that SCG10 is a physiological substrate of PAK4, which is phosphorylated on serine 50 (Ser50) in a PAK4-dependent manner. Phosphorylated SCG10 regulated MT dynamics to promote gastric cancer cell migration and invasion in vitro and metastasis in a xenograft mouse models. Inhibiting PAK4, either by LCH-7749944 or RNA interference, resulted in the inhibition of Ser50 phosphorylation and a blockade to cell invasion, suggesting that PAK4-SCG10 signaling occurs in gastric cancer cell invasion. Moreover, we demonstrated a strong positive correlation between PAK4 and phospho-Ser50 SCG10 expression in gastric cancer samples. We also showed that high expression of SCG10 phospho-Ser50 is highly correlated to an aggressive phenotype of clinical gastric cancer. These findings revealed a novel function of SCG10 in promoting invasive potential of gastric cancer cells, suggesting that blocking PAK4-mediated SCG10 phosphorylation might be a potential therapeutic strategy for metastasis of gastric cancer.

journal_name

Oncogene

journal_title

Oncogene

authors

Guo Q,Su N,Zhang J,Li X,Miao Z,Wang G,Cheng M,Xu H,Cao L,Li F

doi

10.1038/onc.2013.296

subject

Has Abstract

pub_date

2014-06-19 00:00:00

pages

3277-87

issue

25

eissn

0950-9232

issn

1476-5594

pii

onc2013296

journal_volume

33

pub_type

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