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ERp19 contributes to tumorigenicity in human gastric cancer by promoting cell growth, migration and invasion.

Wu J, Chen XH, Wang XQ, Yu Y, Ren JM, Xiao Y, Zhou T, Li P, Xu CD - Oncotarget (2015)

Bottom Line: However, the role of ERp19 in gastric cancer (GC) remains undefined.Furthermore, ERp19 knockdown dramatically suppressed gastric cancer cell growth, inhibited cellular migration/invasion and down regulated the phosphorylation of FAK and paxillin, whereas ERp19 over-expression reversed these changes.ERp19 may represent a new diagnostic and prognostic marker and a novel target for the treatment of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic.

ABSTRACT
ERp19, a mammalian thioredoxin-like protein, plays a key role in defense against endoplasmic reticulum stress. It belongs to the protein disulfide isomerize (PDI) family, whose members have been implicated in development of breast, ovarian and gastrointestinal cancers. However, the role of ERp19 in gastric cancer (GC) remains undefined. Therefore, we sought to investigate the expression and prognostic value of ERp19 in GC patients, and to explore the role of ERp19 in tumorigenicity. Expression of ERp19 in gastric tissues was assessed by immunohistochemical staining and real-time PCR in clinical samples of GC patients. Statistical analysis of clinical cases revealed that the expression levels of ERp19 were higher in tumor tissues than non-tumor tissues. And the level of ERp19 expression was correlated with tumor size, lymph node involvement and poor clinical prognosis. Furthermore, ERp19 knockdown dramatically suppressed gastric cancer cell growth, inhibited cellular migration/invasion and down regulated the phosphorylation of FAK and paxillin, whereas ERp19 over-expression reversed these changes. We conclude that ERp19 contributes to tumorigenicity and metastasis of GC by activating the FAK signaling pathway, and may function as an oncogene in GC. ERp19 may represent a new diagnostic and prognostic marker and a novel target for the treatment of GC.

No MeSH data available.


Related in: MedlinePlus

Effects of ERp19 on cell growth in human gastric cancer cellsA and B, Effects of ERp19 overexpression and knockdown on cell growth using CCK8 assay. (*P < 0.05, **P < 0.01). C and D, Effects of ERp19 overexpression on SGC-7901 cell growth using the plate colony formation assay. The same amounts of SGC-7901/parental, SGC-7901/vector and SGC-7901/ERp19 cells were plated into a 6-well plate. Cell colonies were stained and counted on the 14th day (*P < 0.05). E and F, Effects of ERp19 knockdown on BGC-823 growth using the plate colony formation assay. The data represents mean ± SD of three independent experiments (*P < 0.05).
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Figure 3: Effects of ERp19 on cell growth in human gastric cancer cellsA and B, Effects of ERp19 overexpression and knockdown on cell growth using CCK8 assay. (*P < 0.05, **P < 0.01). C and D, Effects of ERp19 overexpression on SGC-7901 cell growth using the plate colony formation assay. The same amounts of SGC-7901/parental, SGC-7901/vector and SGC-7901/ERp19 cells were plated into a 6-well plate. Cell colonies were stained and counted on the 14th day (*P < 0.05). E and F, Effects of ERp19 knockdown on BGC-823 growth using the plate colony formation assay. The data represents mean ± SD of three independent experiments (*P < 0.05).

Mentions: To examine the role of ERp19 in GC cell growth, we first evaluated cell proliferation by CCK8 assay. As shown in Fig. 3A and 3B, overexpression of ERp19 promoted proliferation, and ERp19 knockdown significantly inhibited cell proliferation. In addition, up-regulation of ERp19 had no effect on proliferation of GES-1 (Fig. S1). Colony formation assays revealed that SGC-7901/ERp19 formed more colonies than control and parental cells (P < 0.05, Fig. 3C and 3D; P < 0.01, Fig. S2A and S2B). Consistently, ERp19 knockdown dramatically suppressed colony formation of BGC-823 cells, in comparison to parental cells and controls (P<0.05, Fig. 3E and 3F; P<0.05 Fig. S2C and S2D). These findings indicate that ERp19 promotes human GC cell growth and proliferation in vitro. We finally wanted to know whether ERp19 could further affect the tumorigenicity in vivo. SGC7901/vector, SGC7901/ERp19, BGC-823/ctrl shRNA and BGC-823/ERp19 shRNA were subcutaneously injected into the nude mice and tumor formation was monitored. On day 30, mice were sacrificed under anesthesia and tumor weights were measured. Tumors grew faster in SGC7901/ERp19 and BGC-823/ctrl shRNA groups compared to the groups of SGC7901/vector and BGC-823/ERp19 shRNA, respectively (Fig. 4A, 4B, 4D and 4E). Furthermore, tumor weights were higher in SGC7901/ERp19 group than that in the group of SGC7901/vector (1.29±0.76 g vs. 0.31± 0.15 g, P < 0.05, Fig. 4C). As expected, compared to BGC-823/ctrl shRNA group, the weight of tumors derived from BGC-823/ERp19 shRNA group was much lower (1.21±0.21 g vs. 0.77±0.23 g, P < 0.05, Fig. 4F). These data suggest that ERp19 could enhance the cell growth in vivo.


ERp19 contributes to tumorigenicity in human gastric cancer by promoting cell growth, migration and invasion.

Wu J, Chen XH, Wang XQ, Yu Y, Ren JM, Xiao Y, Zhou T, Li P, Xu CD - Oncotarget (2015)

Effects of ERp19 on cell growth in human gastric cancer cellsA and B, Effects of ERp19 overexpression and knockdown on cell growth using CCK8 assay. (*P < 0.05, **P < 0.01). C and D, Effects of ERp19 overexpression on SGC-7901 cell growth using the plate colony formation assay. The same amounts of SGC-7901/parental, SGC-7901/vector and SGC-7901/ERp19 cells were plated into a 6-well plate. Cell colonies were stained and counted on the 14th day (*P < 0.05). E and F, Effects of ERp19 knockdown on BGC-823 growth using the plate colony formation assay. The data represents mean ± SD of three independent experiments (*P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494905&req=5

Figure 3: Effects of ERp19 on cell growth in human gastric cancer cellsA and B, Effects of ERp19 overexpression and knockdown on cell growth using CCK8 assay. (*P < 0.05, **P < 0.01). C and D, Effects of ERp19 overexpression on SGC-7901 cell growth using the plate colony formation assay. The same amounts of SGC-7901/parental, SGC-7901/vector and SGC-7901/ERp19 cells were plated into a 6-well plate. Cell colonies were stained and counted on the 14th day (*P < 0.05). E and F, Effects of ERp19 knockdown on BGC-823 growth using the plate colony formation assay. The data represents mean ± SD of three independent experiments (*P < 0.05).
Mentions: To examine the role of ERp19 in GC cell growth, we first evaluated cell proliferation by CCK8 assay. As shown in Fig. 3A and 3B, overexpression of ERp19 promoted proliferation, and ERp19 knockdown significantly inhibited cell proliferation. In addition, up-regulation of ERp19 had no effect on proliferation of GES-1 (Fig. S1). Colony formation assays revealed that SGC-7901/ERp19 formed more colonies than control and parental cells (P < 0.05, Fig. 3C and 3D; P < 0.01, Fig. S2A and S2B). Consistently, ERp19 knockdown dramatically suppressed colony formation of BGC-823 cells, in comparison to parental cells and controls (P<0.05, Fig. 3E and 3F; P<0.05 Fig. S2C and S2D). These findings indicate that ERp19 promotes human GC cell growth and proliferation in vitro. We finally wanted to know whether ERp19 could further affect the tumorigenicity in vivo. SGC7901/vector, SGC7901/ERp19, BGC-823/ctrl shRNA and BGC-823/ERp19 shRNA were subcutaneously injected into the nude mice and tumor formation was monitored. On day 30, mice were sacrificed under anesthesia and tumor weights were measured. Tumors grew faster in SGC7901/ERp19 and BGC-823/ctrl shRNA groups compared to the groups of SGC7901/vector and BGC-823/ERp19 shRNA, respectively (Fig. 4A, 4B, 4D and 4E). Furthermore, tumor weights were higher in SGC7901/ERp19 group than that in the group of SGC7901/vector (1.29±0.76 g vs. 0.31± 0.15 g, P < 0.05, Fig. 4C). As expected, compared to BGC-823/ctrl shRNA group, the weight of tumors derived from BGC-823/ERp19 shRNA group was much lower (1.21±0.21 g vs. 0.77±0.23 g, P < 0.05, Fig. 4F). These data suggest that ERp19 could enhance the cell growth in vivo.

Bottom Line: However, the role of ERp19 in gastric cancer (GC) remains undefined.Furthermore, ERp19 knockdown dramatically suppressed gastric cancer cell growth, inhibited cellular migration/invasion and down regulated the phosphorylation of FAK and paxillin, whereas ERp19 over-expression reversed these changes.ERp19 may represent a new diagnostic and prognostic marker and a novel target for the treatment of GC.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic.

ABSTRACT
ERp19, a mammalian thioredoxin-like protein, plays a key role in defense against endoplasmic reticulum stress. It belongs to the protein disulfide isomerize (PDI) family, whose members have been implicated in development of breast, ovarian and gastrointestinal cancers. However, the role of ERp19 in gastric cancer (GC) remains undefined. Therefore, we sought to investigate the expression and prognostic value of ERp19 in GC patients, and to explore the role of ERp19 in tumorigenicity. Expression of ERp19 in gastric tissues was assessed by immunohistochemical staining and real-time PCR in clinical samples of GC patients. Statistical analysis of clinical cases revealed that the expression levels of ERp19 were higher in tumor tissues than non-tumor tissues. And the level of ERp19 expression was correlated with tumor size, lymph node involvement and poor clinical prognosis. Furthermore, ERp19 knockdown dramatically suppressed gastric cancer cell growth, inhibited cellular migration/invasion and down regulated the phosphorylation of FAK and paxillin, whereas ERp19 over-expression reversed these changes. We conclude that ERp19 contributes to tumorigenicity and metastasis of GC by activating the FAK signaling pathway, and may function as an oncogene in GC. ERp19 may represent a new diagnostic and prognostic marker and a novel target for the treatment of GC.

No MeSH data available.


Related in: MedlinePlus