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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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Effect of CEACAM6 on MMP-9 activity, and cell migratory and invasive ability in GC cells.(A) The supernatant of GC cells was collected after 24 h. Then the MMP-9 activity was examined by gelatin zymography. (B) Relative MMP-9 expression in GC cells. (C, E) Transwell assay. Images show cells that had traveled through the micropore membrane with or without matrigel (200×). (D, F) Histograms showed the numbers of migrating cells and invading cells. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.
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pone-0112908-g004: Effect of CEACAM6 on MMP-9 activity, and cell migratory and invasive ability in GC cells.(A) The supernatant of GC cells was collected after 24 h. Then the MMP-9 activity was examined by gelatin zymography. (B) Relative MMP-9 expression in GC cells. (C, E) Transwell assay. Images show cells that had traveled through the micropore membrane with or without matrigel (200×). (D, F) Histograms showed the numbers of migrating cells and invading cells. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.

Mentions: It is well known that adhesion, degradation and migration are major issues in cancer metastasis. Gelatin zymography was carried out to examine the effects of CEACAM6 on the activity of MMP-9, which is important in ECM degradation. MMP-9 activity in SGC-7901-CEACAM6 and MKN-45-CEACAM6 cells was increased compared with their control groups (Fig. 4A, B). We next investigated whether the increased activity of MMP-9 induced by CEACAM6 in GC cells resulted in a true increment in the number of invading and migrating cells. We thus examined the contribution of active anti-MMP-9 antibody or PBS to CEACAM6-overexpressing GC cells. As expected, there were significant differences in the number of invading and migrating cells in antibody-treated cells compared with PBS-treated cells (P<0.01; Fig. 4C, D, E, F).


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)

Effect of CEACAM6 on MMP-9 activity, and cell migratory and invasive ability in GC cells.(A) The supernatant of GC cells was collected after 24 h. Then the MMP-9 activity was examined by gelatin zymography. (B) Relative MMP-9 expression in GC cells. (C, E) Transwell assay. Images show cells that had traveled through the micropore membrane with or without matrigel (200×). (D, F) Histograms showed the numbers of migrating cells and invading cells. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0112908-g004: Effect of CEACAM6 on MMP-9 activity, and cell migratory and invasive ability in GC cells.(A) The supernatant of GC cells was collected after 24 h. Then the MMP-9 activity was examined by gelatin zymography. (B) Relative MMP-9 expression in GC cells. (C, E) Transwell assay. Images show cells that had traveled through the micropore membrane with or without matrigel (200×). (D, F) Histograms showed the numbers of migrating cells and invading cells. The results are means of three independent experiments in the bar graphs. *P<0.05, **P<0.01.
Mentions: It is well known that adhesion, degradation and migration are major issues in cancer metastasis. Gelatin zymography was carried out to examine the effects of CEACAM6 on the activity of MMP-9, which is important in ECM degradation. MMP-9 activity in SGC-7901-CEACAM6 and MKN-45-CEACAM6 cells was increased compared with their control groups (Fig. 4A, B). We next investigated whether the increased activity of MMP-9 induced by CEACAM6 in GC cells resulted in a true increment in the number of invading and migrating cells. We thus examined the contribution of active anti-MMP-9 antibody or PBS to CEACAM6-overexpressing GC cells. As expected, there were significant differences in the number of invading and migrating cells in antibody-treated cells compared with PBS-treated cells (P<0.01; Fig. 4C, D, E, F).

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