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YAP1 enhances cell proliferation, migration, and invasion of gastric cancer in vitro and in vivo.
Oncotarget. 2016 Dec 06; 7(49):81062-81076.O

Abstract

Yes-associated protein 1 (YAP1) plays an important role in the development of carcinomas such as breast, colorectal, and gastric (GC) cancers, but the role of YAP1 in GC has not been investigated comprehensively. The present study strongly suggests that YAP1 and P62 were significantly up-regulated in GC specimens, compared with normal gastric mucosa. In addition, the YAP1high P62high expression was independently associated with poor prognosis in GC (hazard ratio: 1.334, 95% confidence interval: 1.045-1.704, P = 0.021). Stable YAP1 silencing inhibited the proliferation, migration, and invasion of BGC-823 GC cells in vitro and inhibited the growth of xenograft tumor and hematogenous metastasis of BGC-823 GC cells in vivo. The mechanism was associated with inhibited extracellular signal-regulated kinases (ERK)1/2 phosphorylation, elevated E-cadherin protein expression and decreased vimentin protein expression, down-regulated β-catenin protein expression and elevated α-catenin protein expression, and down-regulated long non-coding RNA (lncRNA) expressions including HOX transcript antisense RNA (HOTAIR), H19, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), human large tumor suppressor-2 (LATS2)-AS1-001, and LATS2. YAP1 over-expression promoted the proliferation, migration, and invasion of human immortalized normal gastric mucosa GES-1 cells in vitro by reversing the above signal molecules. Subcutaneous inoculation of GES-1 cells and YAP1-over-expressing GES-1 cells into nude mice did not generate tumors. We successfully established the xenograft tumor models using MKN-45 GC cells, but immunochemistry showed that there was no YAP1 expression in MKN-45 cells. These results suggest that YAP1 is not a direct factor affecting tumor formation, but could accelerate tumor growth and metastasis. Collectively, this study highlights an important role for YAP1 as a promoter of GC growth and metastasis, and suggests that YAP1 could possibly be a potential treatment target for GC.

Authors+Show Affiliations

Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, 100142, China.Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, 100142, China.Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.Laboratory of Gastrointestinal Onco-Pathology, Cancer Institute and General Surgery Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27835600

Citation

Sun, Dan, et al. "YAP1 Enhances Cell Proliferation, Migration, and Invasion of Gastric Cancer in Vitro and in Vivo." Oncotarget, vol. 7, no. 49, 2016, pp. 81062-81076.
Sun D, Li X, He Y, et al. YAP1 enhances cell proliferation, migration, and invasion of gastric cancer in vitro and in vivo. Oncotarget. 2016;7(49):81062-81076.
Sun, D., Li, X., He, Y., Li, W., Wang, Y., Wang, H., Jiang, S., & Xin, Y. (2016). YAP1 enhances cell proliferation, migration, and invasion of gastric cancer in vitro and in vivo. Oncotarget, 7(49), 81062-81076. https://doi.org/10.18632/oncotarget.13188
Sun D, et al. YAP1 Enhances Cell Proliferation, Migration, and Invasion of Gastric Cancer in Vitro and in Vivo. Oncotarget. 2016 Dec 6;7(49):81062-81076. PubMed PMID: 27835600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - YAP1 enhances cell proliferation, migration, and invasion of gastric cancer in vitro and in vivo. AU - Sun,Dan, AU - Li,Xiaoting, AU - He,Yingjian, AU - Li,Wenhui, AU - Wang,Ying, AU - Wang,Huan, AU - Jiang,Shanshan, AU - Xin,Yan, PY - 2016/03/15/received PY - 2016/10/31/accepted PY - 2016/11/12/pubmed PY - 2018/2/24/medline PY - 2016/11/12/entrez KW - gastric cancer KW - invasion KW - migration KW - proliferation KW - yes-associated protein1/YAP1 SP - 81062 EP - 81076 JF - Oncotarget JO - Oncotarget VL - 7 IS - 49 N2 - Yes-associated protein 1 (YAP1) plays an important role in the development of carcinomas such as breast, colorectal, and gastric (GC) cancers, but the role of YAP1 in GC has not been investigated comprehensively. The present study strongly suggests that YAP1 and P62 were significantly up-regulated in GC specimens, compared with normal gastric mucosa. In addition, the YAP1high P62high expression was independently associated with poor prognosis in GC (hazard ratio: 1.334, 95% confidence interval: 1.045-1.704, P = 0.021). Stable YAP1 silencing inhibited the proliferation, migration, and invasion of BGC-823 GC cells in vitro and inhibited the growth of xenograft tumor and hematogenous metastasis of BGC-823 GC cells in vivo. The mechanism was associated with inhibited extracellular signal-regulated kinases (ERK)1/2 phosphorylation, elevated E-cadherin protein expression and decreased vimentin protein expression, down-regulated β-catenin protein expression and elevated α-catenin protein expression, and down-regulated long non-coding RNA (lncRNA) expressions including HOX transcript antisense RNA (HOTAIR), H19, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), human large tumor suppressor-2 (LATS2)-AS1-001, and LATS2. YAP1 over-expression promoted the proliferation, migration, and invasion of human immortalized normal gastric mucosa GES-1 cells in vitro by reversing the above signal molecules. Subcutaneous inoculation of GES-1 cells and YAP1-over-expressing GES-1 cells into nude mice did not generate tumors. We successfully established the xenograft tumor models using MKN-45 GC cells, but immunochemistry showed that there was no YAP1 expression in MKN-45 cells. These results suggest that YAP1 is not a direct factor affecting tumor formation, but could accelerate tumor growth and metastasis. Collectively, this study highlights an important role for YAP1 as a promoter of GC growth and metastasis, and suggests that YAP1 could possibly be a potential treatment target for GC. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27835600/YAP1_enhances_cell_proliferation_migration_and_invasion_of_gastric_cancer_in_vitro_and_in_vivo_ L2 - https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.13188 DB - PRIME DP - Unbound Medicine ER -