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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 7/2011

Open Access 01-07-2011 | Translational Research and Biomarkers

Inhibition of p600 Expression Suppresses Both Invasiveness and Anoikis Resistance of Gastric Cancer

Authors: Hiroshi Sakai, MD, Kenoki Ohuchida, MD, PhD, Kazuhiro Mizumoto, MD, PhD, Lin Cui, MD, Kohei Nakata, MD, PhD, Hiroki Toma, MD, PhD, Eishi Nagai, MD, PhD, Masao Tanaka, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 7/2011

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Abstract

Background

Advanced gastric cancers often metastasize to distant organs and the peritoneum, leading to a poor prognosis. Both invasiveness and resistance to anchorage-independent cell death (anoikis) are important factors in the process of metastasis. p600 (600-kDa protein), recently identified from a cervical cancer cell line, plays a role in both anoikis resistance and cell migration. In this study, we examined whether p600 is involved in the progression of gastric cancer.

Methods

We used both normal gastric mucosal cells and cancer cells laser-microdissected from 42 gastric cancers and their normal counterparts, and compared their p600 mRNA expression levels with quantitative reverse transcriptase–polymerase chain reaction. We inhibited p600 expression in two gastric cancer cell lines with siRNA and examined its effect on the invasiveness and anoikis resistance both in vitro and in vivo.

Results

Expression of p600 mRNA was significantly higher in gastric cancer cells than in normal mucosal cells (P = 0.027). The invasion assay revealed that invasiveness was significantly reduced by inhibition of p600 (P < 0.01). In vitro experiments revealed that cell viability and colony-formation capacity under anchorage-independent conditions were significantly reduced by inhibition of p600 (P < 0.05). In vivo experiments also showed that the establishment of intraperitoneal disseminated tumors was significantly suppressed by transient inhibition of p600 (P < 0.001).

Conclusions

Our results strongly suggest that p600 is involved in gastric cancer progression, and has a potential to be a new molecular target for gastric cancer therapy.
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Metadata
Title
Inhibition of p600 Expression Suppresses Both Invasiveness and Anoikis Resistance of Gastric Cancer
Authors
Hiroshi Sakai, MD
Kenoki Ohuchida, MD, PhD
Kazuhiro Mizumoto, MD, PhD
Lin Cui, MD
Kohei Nakata, MD, PhD
Hiroki Toma, MD, PhD
Eishi Nagai, MD, PhD
Masao Tanaka, MD, PhD, FACS
Publication date
01-07-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 7/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1523-0

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