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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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Effects of CEACAM6 on cell morphology and cytoskeleton in GC cells.(A) Stable overexpression and suppression of CEACAM6 in GC cells. (B) CEACAM6 expression was analyzed by immunofluorescence, and more CEACAM6 expression was detected in CEACAM6-overexpressing cells than that in control cells (200×). Blue: DAPI; red: CEACAM6. (C) Overexpression of CEACAM6 in SGC-7901 and MKN-45 cells induced a mesenchymal morphology, whereas knockdown of CEACAM6 in MKN-28 cells induced an epithelial morphology (200×). (D) Immunostaining of F-actin in CEACAM6-overexpressing cells and control cells (400×). Red: F-actin; blue: DAPI.
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pone-0112908-g001: Effects of CEACAM6 on cell morphology and cytoskeleton in GC cells.(A) Stable overexpression and suppression of CEACAM6 in GC cells. (B) CEACAM6 expression was analyzed by immunofluorescence, and more CEACAM6 expression was detected in CEACAM6-overexpressing cells than that in control cells (200×). Blue: DAPI; red: CEACAM6. (C) Overexpression of CEACAM6 in SGC-7901 and MKN-45 cells induced a mesenchymal morphology, whereas knockdown of CEACAM6 in MKN-28 cells induced an epithelial morphology (200×). (D) Immunostaining of F-actin in CEACAM6-overexpressing cells and control cells (400×). Red: F-actin; blue: DAPI.

Mentions: Our previous results implied that MKN-28 GC cells inherently express high levels of CEACAM6, whereas SGC-7901 and MKN-45 GC cells express low levels [12]. Overexpression of CEACAM6 in SGC-7901 and MKN-45 GC cells and attenuation of CEACAM6 expression in MKN-28 GC cells by pL/shRNA/shR-CEACAM6 lentiviral vectors were confirmed at the protein level by western blot analysis (Fig. 1A). Immunofluorescence assays always showed that SGC-7901-CEACAM6 cells expressed more CEACAM6 protein than SGC-7901-NC cells (Fig. 1B).


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)

Effects of CEACAM6 on cell morphology and cytoskeleton in GC cells.(A) Stable overexpression and suppression of CEACAM6 in GC cells. (B) CEACAM6 expression was analyzed by immunofluorescence, and more CEACAM6 expression was detected in CEACAM6-overexpressing cells than that in control cells (200×). Blue: DAPI; red: CEACAM6. (C) Overexpression of CEACAM6 in SGC-7901 and MKN-45 cells induced a mesenchymal morphology, whereas knockdown of CEACAM6 in MKN-28 cells induced an epithelial morphology (200×). (D) Immunostaining of F-actin in CEACAM6-overexpressing cells and control cells (400×). Red: F-actin; blue: DAPI.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112908-g001: Effects of CEACAM6 on cell morphology and cytoskeleton in GC cells.(A) Stable overexpression and suppression of CEACAM6 in GC cells. (B) CEACAM6 expression was analyzed by immunofluorescence, and more CEACAM6 expression was detected in CEACAM6-overexpressing cells than that in control cells (200×). Blue: DAPI; red: CEACAM6. (C) Overexpression of CEACAM6 in SGC-7901 and MKN-45 cells induced a mesenchymal morphology, whereas knockdown of CEACAM6 in MKN-28 cells induced an epithelial morphology (200×). (D) Immunostaining of F-actin in CEACAM6-overexpressing cells and control cells (400×). Red: F-actin; blue: DAPI.
Mentions: Our previous results implied that MKN-28 GC cells inherently express high levels of CEACAM6, whereas SGC-7901 and MKN-45 GC cells express low levels [12]. Overexpression of CEACAM6 in SGC-7901 and MKN-45 GC cells and attenuation of CEACAM6 expression in MKN-28 GC cells by pL/shRNA/shR-CEACAM6 lentiviral vectors were confirmed at the protein level by western blot analysis (Fig. 1A). Immunofluorescence assays always showed that SGC-7901-CEACAM6 cells expressed more CEACAM6 protein than SGC-7901-NC cells (Fig. 1B).

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