ERp29 controls invasion and metastasis of gastric carcinoma by inhibition of epithelial-mesenchymal transition via PI3K/Aktsignaling pathway

• Published in: BMC cancer 2017-09, Vol.17 (1), p.626-626, Article 626
• Main Authors: Ye, Jianxin, Huang, Jinsheng, Xu, Jie, Huang, Qiang, Wang, Jinzhou, Zhong, Wenjing, Lin, Xinjian, Li, Yun, Lin, Xu
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adult; Aged; AKT; AKT protein; Animals; Arthritis; Breast cancer; Cancer metastasis; Cancer therapies; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Chemotherapy; Disease Models, Animal; Ectopic Gene Expression; Endoplasmic reticulum; Epidermal growth factor; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - genetics; ERp29; Female; Gastric cancer; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Health aspects; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Heterografts; Humans; Immunoglobulins; Kinases; Male; Malignancy; Medical prognosis; Mesenchyme; Metastases; Metastasis; Mice; Middle Aged; Molecular modelling; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Phosphatidylinositol 3-Kinases - metabolism; PI3K; Prognosis; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Stem cells; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tumor suppressor genes; Tumorigenesis; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-017-3613-x

Gastric cancer (GC) accounts for the fourth most occurring malignancy and the third major cause of cancer death. Identifying novel molecular signaling pathways participating in gastric tumorigenesis and progression is pivotal for rational design of targeted therapies to improve advanced GC outcome. Recently, the endoplasmic reticulum (ER) protein 29 (ERp29) has been shown to inversely associate with primary tumor development and function as a tumor suppressor in breast cancer. However, the role of ERp29 in GC patients' prognosis and its function in GC progression is unknown. Clinical importance of ERp29 in the prognosis of GC patients was assessed by examining its expression in 148 GC tumor samples and correlation with clinicopathological characteristics and survival of the patients. The function and underlying mechanisms of ERp29 in GC growth, invasion and metastasis were explored both in vitro and in vivo. Downregulation of ERp29 was commonly found in GC tissues and highly correlated with more aggressive phenotypes and poorer prognosis. Functional assays demonstrated that knockdown of ERp29 increased GC cell migration and invasion and promoted metastasis. Conversely, ectopic overexpression of ERp29 produced opposite effects. Mechanistic studies revealed that loss of ERp29 induced an epithelial-to-mesenchymal transition (EMT) in the GC cells through activation of PI3K/Akt pathway signaling. These findings suggest that downregulation of ERp29 is probably one of the key molecular mechanisms responsible for the development and progression of GC.