EGFR-induced phosphorylation of type Iγ phosphatidylinositol phosphate kinase promotes pancreatic cancer progression

Chunhua Chen, Xiangling Wang, Juemin Fang, Junli Xue, Xunhao Xiong, Yan Huang, Jinghua Hu, Kun Ling

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Pancreatic cancer is one of the deadliest malignancies and effective treatment has always been lacking. In current study, we investigated how the type Iγ phosphatidylinositol phosphate kinase (PIPKIγ) participates in the progression of pancreatic ductal adenocarcinoma (PDAC) for novel therapeutic potentials against this lethal disease. We found that PIPKIγ is up-regulated in all tested PDAC cell lines. The growth factor (including EGFR)-induced tyrosine phosphorylation of PIPKIγ is significantly elevated in in situ and metastatic PDAC tissues. Loss of PIPKIγ inhibits the aggressiveness of PDAC cells by restraining the activities of AKT and STAT3, as well as MT1-MMP expression. Therefore when planted into the pancreas of nude mice, PIPKIγ-depleted PDAC cells exhibits substantially repressed tumor growth and metastasis comparing to control PDAC cells. Results from further studies showed that the phosphorylation-deficient PIPKIγ mutant, unlike its wild-type counterpart, cannot rescue PDAC progression inhibited by PIPKIγ depletion. These findings indicate that PIPKIγ, functioning downstream of EGFR signaling, is critical to the progression of PDAC, and suggest that PIPKIγ is potentially a valuable therapeutic target for PDAC treatment.

Original languageEnglish (US)
Pages (from-to)42621-42637
Number of pages17
JournalOncotarget
Volume8
Issue number26
DOIs
StatePublished - 2017

Fingerprint

Phosphatidylinositol Phosphates
Pancreatic Neoplasms
Adenocarcinoma
Phosphotransferases
Phosphorylation
Matrix Metalloproteinase 14
Nude Mice
Tyrosine
Pancreas
Neoplasms
Intercellular Signaling Peptides and Proteins
Neoplasm Metastasis
Cell Line

Keywords

  • EGFR
  • Metastasis
  • Pancreatic cancer
  • Type Iγ phosphatidylinositol phosphate kinase
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Oncology

Cite this

EGFR-induced phosphorylation of type Iγ phosphatidylinositol phosphate kinase promotes pancreatic cancer progression. / Chen, Chunhua; Wang, Xiangling; Fang, Juemin; Xue, Junli; Xiong, Xunhao; Huang, Yan; Hu, Jinghua; Ling, Kun.

In: Oncotarget, Vol. 8, No. 26, 2017, p. 42621-42637.

Research output: Contribution to journalArticle

Chen, Chunhua ; Wang, Xiangling ; Fang, Juemin ; Xue, Junli ; Xiong, Xunhao ; Huang, Yan ; Hu, Jinghua ; Ling, Kun. / EGFR-induced phosphorylation of type Iγ phosphatidylinositol phosphate kinase promotes pancreatic cancer progression. In: Oncotarget. 2017 ; Vol. 8, No. 26. pp. 42621-42637.
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