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CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway.

Zang M, Zhang B, Zhang Y, Li J, Su L, Zhu Z, Gu Q, Liu B, Yan M - PLoS ONE (2014)

Bottom Line: Overexpressed CEACAM6 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT markers N-cadherin, Vimentin and Slug while E-cadherin expression was decreased in CEACAM6-overexpressing GC cells; opposing results were observed in CEACAM6-silenced cells.We further observed that LY294002, a PI3K inhibitor, could reverse CEACAM6-induced EMT via mesenchymal-epithelial transition.These findings suggest that CEACAM6 enhances invasion and metastasis in GC by promoting EMT via the PI3K/AKT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Overexpressed CEACAM6 in tumor tissues plays important roles in invasion, metastasis and anoikis resistance in a variety of human cancers. We recently reported that CEACAM6 expression is upregulated in Gastric cancer (GC) tissues and promoted GC metastasis. Here, we report that CEACAM6 promotes peritoneal metastases in vivo and is negatively correlated with E-cadherin expression in GC tissues. Overexpressed CEACAM6 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT markers N-cadherin, Vimentin and Slug while E-cadherin expression was decreased in CEACAM6-overexpressing GC cells; opposing results were observed in CEACAM6-silenced cells. Furthermore, E-cadherin expression was negatively correlated with depth of tumor invasion, lymph node metastasis and TNM stage in GC tissues. Additionally, CEACAM6 elevated matrix metalloproteinase-9 (MMP-9) activity in GC, and anti-MMP-9 antibody could reverse the increasing invasion and migration induced by CEACAM6. CEACAM6 also increased the levels of phosphorylated AKT, which is involved in the progression of a variety of human tumors. We further observed that LY294002, a PI3K inhibitor, could reverse CEACAM6-induced EMT via mesenchymal-epithelial transition. These findings suggest that CEACAM6 enhances invasion and metastasis in GC by promoting EMT via the PI3K/AKT signaling pathway.

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CEACAM6 induces EMT in GC.(A, C) The protein levels of EMT markers were assayed by western blot analysis in GC cells with CEACAM6 overexpression or knockdown. (B, D) Relative EMT marker expression in CEACAM6-overexpressing and -silenced GC cells were calculated by gray scale ratio. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.
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pone-0112908-g003: CEACAM6 induces EMT in GC.(A, C) The protein levels of EMT markers were assayed by western blot analysis in GC cells with CEACAM6 overexpression or knockdown. (B, D) Relative EMT marker expression in CEACAM6-overexpressing and -silenced GC cells were calculated by gray scale ratio. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.

Mentions: EMT-related proteins in GC cells were evaluated by western blot analysis. We observed that the N-cadherin, Vimentin and Slug protein levels were increased, while E-cadherin was decreased in CEACAM6-overexpressing cells compared with their respective control cells (Fig. 3A, B). Converse results were obtained after CEACAM6 was knocked down in MKN-28 cells (Fig. 3C, D). These results suggested a functional role for CEACAM6 in regulating EMT in GC cells. Moreover, these observations in GC cells were similar with the findings in GC tissue.


CEACAM6 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition via PI3K/AKT signaling pathway.

Zang M, Zhang B, Zhang Y, Li J, Su L, Zhu Z, Gu Q, Liu B, Yan M - PLoS ONE (2014)

CEACAM6 induces EMT in GC.(A, C) The protein levels of EMT markers were assayed by western blot analysis in GC cells with CEACAM6 overexpression or knockdown. (B, D) Relative EMT marker expression in CEACAM6-overexpressing and -silenced GC cells were calculated by gray scale ratio. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4232574&req=5

pone-0112908-g003: CEACAM6 induces EMT in GC.(A, C) The protein levels of EMT markers were assayed by western blot analysis in GC cells with CEACAM6 overexpression or knockdown. (B, D) Relative EMT marker expression in CEACAM6-overexpressing and -silenced GC cells were calculated by gray scale ratio. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.
Mentions: EMT-related proteins in GC cells were evaluated by western blot analysis. We observed that the N-cadherin, Vimentin and Slug protein levels were increased, while E-cadherin was decreased in CEACAM6-overexpressing cells compared with their respective control cells (Fig. 3A, B). Converse results were obtained after CEACAM6 was knocked down in MKN-28 cells (Fig. 3C, D). These results suggested a functional role for CEACAM6 in regulating EMT in GC cells. Moreover, these observations in GC cells were similar with the findings in GC tissue.

Bottom Line: Overexpressed CEACAM6 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT markers N-cadherin, Vimentin and Slug while E-cadherin expression was decreased in CEACAM6-overexpressing GC cells; opposing results were observed in CEACAM6-silenced cells.We further observed that LY294002, a PI3K inhibitor, could reverse CEACAM6-induced EMT via mesenchymal-epithelial transition.These findings suggest that CEACAM6 enhances invasion and metastasis in GC by promoting EMT via the PI3K/AKT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.

ABSTRACT
Overexpressed CEACAM6 in tumor tissues plays important roles in invasion, metastasis and anoikis resistance in a variety of human cancers. We recently reported that CEACAM6 expression is upregulated in Gastric cancer (GC) tissues and promoted GC metastasis. Here, we report that CEACAM6 promotes peritoneal metastases in vivo and is negatively correlated with E-cadherin expression in GC tissues. Overexpressed CEACAM6 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT markers N-cadherin, Vimentin and Slug while E-cadherin expression was decreased in CEACAM6-overexpressing GC cells; opposing results were observed in CEACAM6-silenced cells. Furthermore, E-cadherin expression was negatively correlated with depth of tumor invasion, lymph node metastasis and TNM stage in GC tissues. Additionally, CEACAM6 elevated matrix metalloproteinase-9 (MMP-9) activity in GC, and anti-MMP-9 antibody could reverse the increasing invasion and migration induced by CEACAM6. CEACAM6 also increased the levels of phosphorylated AKT, which is involved in the progression of a variety of human tumors. We further observed that LY294002, a PI3K inhibitor, could reverse CEACAM6-induced EMT via mesenchymal-epithelial transition. These findings suggest that CEACAM6 enhances invasion and metastasis in GC by promoting EMT via the PI3K/AKT signaling pathway.

Show MeSH
Related in: MedlinePlus