Oncotarget

Research Papers:

KIAA1199 is induced by inflammation and enhances malignant phenotype in pancreatic cancer

Shiro Kohi _, Norihiro Sato, Atsuhiro Koga, YNobutaka Matayoshi and Keiji Hirata

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:17156-17163. https://doi.org/10.18632/oncotarget.15052

Metrics: PDF 1016 views  |   HTML 1381 views  |   ?  


Abstract

Shiro Kohi1, Norihiro Sato1, Atsuhiro Koga1, Nobutaka Matayoshi1, Keiji Hirata1

1Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Fukuoka 807-8555, Japan

Correspondence to:

Norihiro Sato, email: norisato@med.uoeh-u.ac.jp

Keywords: pancreatic cancer, KIAA1199, hyaluronan, migration, inflammation

Received: November 16, 2016     Accepted: January 11, 2017     Published: February 04, 2017

ABSTRACT

Background: Recent evidence suggests a critical role of hyaluronan (HA), especially low-molecular-weight HA (LMW-HA), in the aggressive tumor phenotype. Increased expression of KIAA1199, a newly identified protein involved in HA degradation, has been reported in various cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the functional significance of KIAA1199 in PDAC.

Methods: Using siRNA knockdown and forced expression models, we investigated the effects of KIAA1199 expression on malignant behaviors (proliferation, migration, and invasion) of PDAC cells. We also examined the effect of inflammation on the transcriptional regulation of KIAA1199 using a pro-inflammatory cytokine and anti-inflammatory agent.

Results: Knockdown of KIAA1199 expression using siRNA resulted in decreased cell migration and proliferation. On the other hand, forced expression of KIAA1199 using gene transduction significantly enhanced the migration and invasion. Importantly, increased KIAA1199 expression was associated with an increased level of LMW-HA in the conditioned medium. Exposure to a pro-inflammatory cytokine, interleukin-1ß, increased the KIAA1199 transcription and enhanced the migration. In contrast, treatment with NS-398, a cyclooxygenase-2 inhibitor, decreased the KIAA1199 expression and inhibited the migration.

Conclusions: These findings suggest that increased KIAA1199 expression may contribute to the aggressive phenotype partly through increasing the LMW-HA concentration. Our present results also suggest a possible link between inflammation, induced KIAA1199 expression, and enhanced migration during PDAC progression.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 15052