Overexpression of KIF11 in Gastric Cancer with Intestinal Mucin Phenotype

Abstract

Objective: Gastric cancer (GC) is one of the most common human cancers. A useful method of gastric cancer stem cell (CSC) characterization is spheroid colony formation. Previously, we reported that KIF11 expression is >2-fold in spheroid-body-forming GC cells compared with parental cells. Here, we analyzed the expression and distribution of KIF11 in human GC by immunohistochemistry. Methods: Expression of KIF11 in 165 GC cases was determined using immunohistochemistry. For mucin phenotypic expression analysis of GC, immunostaining of MUC5AC, MUC6, MUC2 and CD10 was evaluated. RNA interference was used to inhibit KIF11 expression in GC cell lines. Results: In total, 119 of 165 GC cases (72%) were positive for KIF11. Expression of KIF11 was not associated with any clinicopathologic characteristics; however, it was observed frequently in GC exhibiting an intestinal phenotype. Both the number and size of spheres formed by MKN-74 cells were significantly reduced following transfection of KIF11-targeting siRNA compared with negative-control siRNA. Furthermore, levels of phosphorylated Erk1/2 were lower in KIF11 siRNA-transfected cells than with negative-control siRNA-transfected cells. Conclusion: These results indicate that KIF11 is involved in intestinal mucin phenotype GC.

KIF11 Is Required for Spheroid Formation by Oesophageal and Colorectal Cancer Cells

“…We also reported that KIF11 likely plays an important role in gastric CSCs (6). In the present study, we found that both the number and size of spheres produced by ESCC and CRC cell lines were significantly reduced by KIF11 siRNA transfection compared with negative control siRNA-transfected cells, indicating that KIF11 is required for sphere formation of ESCC and CRC cells.…”

“…Previously, we reported that KIF11 protein expression is upregulated in 72% of GC cases and that KIF11 is involved in spheroid formation (6). In the present study, we analyzed KIF11 expression in ESCC and CRC tissues.…”

“…), and 1 μg of total RNA was converted to cDNA using First Strand cDNA Synthesis Kit (Amersham Biosciences, Piscataway, NJ, USA). Quantitation of KIF11 mRNA level was performed by real-time fluorescence detection as described previously (6). PCR was conducted using the SYBR Green PCR Core Reagents Kit (Applied Biosystems).…”

“…We previously showed that KIF11 and kinesin family C1 (KIFC1) genes are more highly expressed, by more than two-fold, in spheroid-forming cells than in the parental cells of GC cell lines (5). We also showed that KIF11 protein expression is upregulated in GC tissue samples, and that both the number and size of spheres produced by GC cells are significantly reduced by inhibition of KIF11 (6). These results suggest that KIF11 likely plays an important role in gastric CSCs.…”

Identification of Candidate Targeted Genes in Molecular Subtypes of Gastric Cancer

“…KIF11 was overexpression in gastric cancer. Knockdown of KIF11 inhibited sphere formation of gastric cancer stem cells, so KIF11 likely played a vital role in gastric cancer [14].…”