The catalytically defective receptor protein tyrosine kinase EphA10 promotes tumorigenesis in pancreatic cancer cells

Won Sik Shin, Mi Kyung Park, Young Hun Lee, Kyung Woo Kim, Ho Lee, Seung Taek Lee

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

EphA10 (erythropoietin-producing hepatocellular carcinoma receptor A10) is a catalytically defective receptor protein tyrosine kinase in the ephrin receptor family. Although EphA10 is involved in the malignancy of some types of cancer, its role as an oncogene has not been extensively studied. Here, we investigated the influence of EphA10 on the tumorigenic potential of pancreatic cancer cells. Analysis of expression profiles from The Cancer Genome Atlas confirmed that EphA10 was elevated and higher in tumor tissues than in normal tissues in some cancer types, including pancreatic cancer. EphA10 silencing reduced the proliferation, migration, and adhesion of MIA PaCa-2 and AsPC-1 pancreatic cancer cells. These effects were reversed by overexpression of EphA10 in MIA PaCa-2 cells. Importantly, overexpression and silencing of EphA10 respectively increased and decreased the weight, volume, and number of Ki-67-positive proliferating cells in MIA PaCa-2 xenograft tumors. Further, EphA10 expression was positively correlated with invasion and gelatin degradation in MIA PaCa-2 cells. Moreover, overexpression of EphA10 enhanced the expression and secretion of MMP-9 in MIA PaCa-2 cells and increased the expression of MMP-9 and the vascular density in xenograft tumors. Finally, expression of EphA10 increased the phosphorylation of ERK, JNK, AKT, FAK, and NF-κB, which are important for cell proliferation, survival, adhesion, migration, and invasion. Therefore, we suggest that EphA10 plays a pivotal role in the tumorigenesis of pancreatic epithelial cells and is a novel therapeutic target for pancreatic cancer.

Original languageEnglish
Pages (from-to)3292-3302
Number of pages11
JournalCancer Science
Volume111
Issue number9
DOIs
Publication statusPublished - 2020 Sept 1

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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