Overexpression of stromal interaction molecule 1 may promote epithelial‑mesenchymal transition and indicate poor prognosis in gastric cancer

Wu,Guobin; Li,Yong; Tan,Bibo; Fan,Liqiao; Zhao,Qun; Liu,Yü; Zhang,Zhidong

doi:10.3892/mmr.2017.6607

Overexpression of stromal interaction molecule 1 may promote epithelial‑mesenchymal transition and indicate poor prognosis in gastric cancer

Authors:
- Guobin Wu
- Yong Li
- Bibo Tan
- Liqiao Fan
- Qun Zhao
- Yü Liu
- Zhidong Zhang
View Affiliations

Affiliations: Department of General Surgery, The Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: May 18, 2017 https://doi.org/10.3892/mmr.2017.6607
Pages: 151-158
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the present study was to investigate the prognostic significance of stromal interaction molecule 1 (STIM1) expression in gastric cancer (GC) and examine the association between STIM1 and epithelial‑mesenchymal transition (EMT). Immunohistochemical staining was performed to detect STIM1, E‑cadherin, β‑catenin and matrix metalloproteinase‑9 (MMP‑9) in 170 GC and 35 adjacent healthy gastric tissue samples. Positive staining of STIM1, E‑cadherin, β‑catenin and MMP‑9 in GC tissues was significantly greater compared with adjacent healthy tissues (P<0.05). Clinicopathological analysis revealed that STIM1 expression was significantly associated with LNM (P<0.001) and tumor‑node‑metastasis stage (P=0.01). The overall survival rate was significantly reduced in STIM1‑positive compared with STIM1‑negative patients (P=0.043). Cox regression analysis indicated that STIM1 expression and LNM were independent prognostic factors for GC. Chi‑square tests suggested that STIM1 expression in GC tissues was significantly associated with E‑cadherin (P<0.001) and β‑catenin (P<0.001), whereas no association was observed between STIM1 and MMP‑9 expression (P>0.05). In conclusion, the results of the present study suggested that STIM1 may be a valuable prognostic marker in GC patients, and that STIM1 may increase GC motility and invasiveness by promoting epithelial‑mesenchymal transition.

View Figures

View References

1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
2	Suzuki R, Yamamoto E, Nojima M, Maruyama R, Yamano HO, Yoshikawa K, Kimura T, Harada T, Ashida M, Niinuma T, et al: Aberrant methylation of microRNA-34b/c is a predictive marker of metachronous gastric cancer risk. J Gastroenterol. 49:1135–1144. 2014. View Article : Google Scholar : PubMed/NCBI
3	Bria E, De Manzoni G, Beghelli S, Tomezzoli A, Barbi S, Di Gregorio C, Scardoni M, Amato E, Frizziero M, Sperduti I, et al: A clinical-biological risk stratification model for resected gastric cancer: Prognostic impact of Her2, Fhit, and APC expression status. Ann Oncol. 24:693–701. 2013. View Article : Google Scholar : PubMed/NCBI
4	Kraljevic Pavelic S, Sedic M, Bosnjak H, Spaventi S and Pavelic K: Metastasis: New perspectives on an old problem. Mol Cancer. 10:222011. View Article : Google Scholar : PubMed/NCBI
5	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
6	Thiery JP and Sleeman JP: Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 7:131–142. 2006. View Article : Google Scholar : PubMed/NCBI
7	Savagner P, Boyer B, Valles AM, Jouanneau J and Thiery JP: Modulations of the epithelial phenotype during embryogenesis and cancer progression. Cancer Treat Res. 71:229–249. 1994. View Article : Google Scholar : PubMed/NCBI
8	Tam WL and Weinberg RA: The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med. 19:1438–1449. 2013. View Article : Google Scholar : PubMed/NCBI
9	Liu J, Chen X, Ward T, Pegram M and Shen K: Combined niclosamide with cisplatin inhibits epithelial-mesenchymal transition and tumor growth in cisplatin-resistant triple-negative breast cancer. Tumour Biol. 37:9825–9835. 2016. View Article : Google Scholar : PubMed/NCBI
10	Luo M, Hou L, Li J, Shao S, Huang S, Meng D, Liu L, Feng L, Xia P, Qin T and Zhao X: VEGF/NRP-1axis promotes progression of breast cancer via enhancement of epithelial-mesenchymal transition and activation of NF-κB and β-catenin. Cancer Lett. 373:1–11. 2016. View Article : Google Scholar : PubMed/NCBI
11	Ma J, Zhao J, Lu J, Wang P, Feng H, Zong Y, Ou B, Zheng M and Lu A: Cadherin-12 enhances proliferation in colorectal cancer cells and increases progression by promoting EMT. Tumour Biol. 37:9077–9088. 2016. View Article : Google Scholar : PubMed/NCBI
12	Bruyere F, Namdarian B, Corcoran NM, Pedersen J, Ockrim J, Voelzke BB, Mete U, Costello AJ and Hovens CM: Snail expression is an independent predictor of tumor recurrence in superficial bladder cancers. Urol Oncol. 28:591–596. 2010. View Article : Google Scholar : PubMed/NCBI
13	Chiu KY, Wu CC, Chia CH, Hsu SL and Tzeng YM: Inhibition of growth, migration and invasion of human bladder cancer cells by antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, and its molecular mechanisms. Cancer Lett. 373:174–184. 2016. View Article : Google Scholar : PubMed/NCBI
14	Lee SO, Yang X, Duan S, Tsai Y, Strojny LR, Keng P and Chen Y: IL-6 promotes growth and epithelial-mesenchymal transition of CD133+ cells of non-small cell lung cancer. Oncotarget. 7:6626–6638. 2016.PubMed/NCBI
15	Huang L, Wu RL and Xu AM: Epithelial-mesenchymal transition in gastric cancer. Am J Transl Res. 7:2141–2158. 2015.PubMed/NCBI
16	Parekh AB: Store-operated CRAC channels: Function in health and disease. Nat Rev Drug Discov. 9:399–410. 2010. View Article : Google Scholar : PubMed/NCBI
17	Chen YF, Chiu WT, Chen YT, Lin PY, Huang HJ, Chou CY, Chang HC, Tang MJ and Shen MR: Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an important role in cervical cancer growth, migration, and angiogenesis. Proc Natl Acad Sci USA. 108:15225–15230. 2011. View Article : Google Scholar : PubMed/NCBI
18	Yang S, Zhang JJ and Huang XY: Orai1 and STIM1 are critical for breast tumor cell migration and metastasis. Cancer Cell. 15:124–134. 2009. View Article : Google Scholar : PubMed/NCBI
19	Hu J, Qin K, Zhang Y, Gong J, Li N, Lv D, Xiang R and Tan X: Downregulation of transcription factor Oct4 induces an epithelial-to-mesenchymal transition via enhancement of Ca2+ influx in breast cancer cells. Biochem Biophys Res Commun. 411:786–791. 2011. View Article : Google Scholar : PubMed/NCBI
20	Zhang Z, Liu X, Feng B, Liu N, Wu Q, Han Y, Nie Y, Wu K, Shi Y and Fan D: STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer. Oncogene. 34:4808–4820. 2015. View Article : Google Scholar : PubMed/NCBI
21	Casas-Rua V, Tomas-Martin P, Lopez-Guerrero AM, Alvarez IS, Pozo-Guisado E and Martin-Romero FJ: STIM1 phosphorylation triggered by epidermal growth factor mediates cell migration. Biochim Biophys Acta. 1853:233–243. 2015. View Article : Google Scholar : PubMed/NCBI
22	Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Handbook. Chicago: Springer-Verlag New York; 2010
23	World Health Organization Classification of Tumours: Pathology and genetics of tumours of the digestive system. Lyon: IARC Press; 2000
24	Wang JY, Sun J, Huang MY, Wang YS, Hou MF, Sun Y, He H, Krishna N, Chiu SJ, Lin S, et al: STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression. Oncogene. 34:4358–4367. 2015. View Article : Google Scholar : PubMed/NCBI
25	Chaw SY, Majeed AA, Dalley AJ, Chan A, Stein S and Farah CS: Epithelial to mesenchymal transition (EMT) biomarkers-E-cadherin, beta-catenin, APC and Vimentin-in oral squamous cell carcinogenesis and transformation. Oral Oncol. 48:997–1006. 2012. View Article : Google Scholar : PubMed/NCBI
26	Ouadid-Ahidouch H, Dhennin-Duthille I, Gautier M, Sevestre H and Ahidouch A: TRP channels: Diagnostic markers and therapeutic targets for breast cancer? Trends Mol Med. 19:117–124. 2013. View Article : Google Scholar : PubMed/NCBI
27	Prevarskaya N, Skryma R and Shuba Y: Calcium in tumour metastasis: New roles for known actors. Nat Rev Cancer. 11:609–618. 2011. View Article : Google Scholar : PubMed/NCBI
28	Bergmeier W, Weidinger C, Zee I and Feske S: Emerging roles of store-operated Ca²⁺ entry through STIM and ORAI proteins in immunity, hemostasis and cancer. Channels (Austin). 7:379–391. 2013. View Article : Google Scholar : PubMed/NCBI
29	Liu H, Hughes JD, Rollins S, Chen B and Perkins E: Calcium entry via ORAI1 regulates glioblastoma cell proliferation and apoptosis. Exp Mol Pathol. 91:753–760. 2011. View Article : Google Scholar : PubMed/NCBI
30	Wong HS and Chang WC: Correlation of clinical features and genetic profiles of stromal interaction molecule 1 (STIM1) in colorectal cancers. Oncotarget. 6:42169–42182. 2015.PubMed/NCBI
31	Li Y, Guo B, Xie Q, Ye D, Zhang D, Zhu Y, Chen H and Zhu B: STIM1 Mediates Hypoxia-Driven Hepatocarcinogenesis via Interaction with HIF-1. Cell Rep. 12:388–395. 2015. View Article : Google Scholar : PubMed/NCBI
32	Sabbioni S, Barbanti-Brodano G, Croce CM and Negrini M: GOK: A gene at 11p15 involved in rhabdomyosarcoma and rhabdoid tumor development. Cancer Res. 57:4493–4497. 1997.PubMed/NCBI
33	Sabbioni S, Veronese A, Trubia M, Taramelli R, Barbanti-Brodano G, Croce CM and Negrini M: Exon structure and promoter identification of STIM1 (alias GOK), a human gene causing growth arrest of the human tumor cell lines G401 and RD. Cytogenet Cell Genet. 86:214–218. 1999. View Article : Google Scholar : PubMed/NCBI
34	Suyama E, Wadhwa R, Kaur K, Miyagishi M, Kaul SC, Kawasaki H and Taira K: Identification of metastasis-related genes in a mouse model using a library of randomized ribozymes. J Biol Chem. 279:38083–38086. 2004. View Article : Google Scholar : PubMed/NCBI
35	Weidinger C, Shaw PJ and Feske S: STIM1 and STIM2-mediated Ca(2+) influx regulates antitumour immunity by CD8(+) T cells. EMBO Mol Med. 5:1311–1321. 2013. View Article : Google Scholar : PubMed/NCBI