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Rap1A promotes esophageal squamous cell carcinoma metastasis through the AKT signaling pathway.

ABSTRACT: Ras‑associated protein 1A (Rap1A) is a member of the Ras subfamily of small GTP‑binding proteins and is found to promote metastasis in several types of cancer. However, the functional role and molecular mechanism of action in Rap1A in esophageal squamous cell carcinoma (ESCC) is not fully understood. In the present study, Rap1A was found to be upregulated in ESCC tissues and its expression was correlated with cancer stage. Functional studies revealed that Rap1A could promote ESCC metastasis by stimulating cell migration and invasion in vivo and in vitro. Further study indicated that the transcriptional factor SP1 increased Rap1A expression via promoter binding and transcription activation. Furthermore, Rap1A promoted epithelial‑to‑mesenchymal transition, possibly through the AKT signaling pathway. Hence, the findings of the present study indicated that Rap1A may be a potential prognostic marker or therapeutic target for ESCC.

SUBMITTER: Li Q

PROVIDER: S-EPMC6775818 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Rap1A promotes esophageal squamous cell carcinoma metastasis through the AKT signaling pathway.

Li Qinfang Q Xu Aiping A Chu Yuan Y Chen Tao T Li Hongqi H Yao Liqing L Zhou Pinghong P Xu Meidong M

Oncology reports 20190912 5

Ras‑associated protein 1A (Rap1A) is a member of the Ras subfamily of small GTP‑binding proteins and is found to promote metastasis in several types of cancer. However, the functional role and molecular mechanism of action in Rap1A in esophageal squamous cell carcinoma (ESCC) is not fully understood. In the present study, Rap1A was found to be upregulated in ESCC tissues and its expression was correlated with cancer stage. Functional studies revealed that Rap1A could promote ESCC metastasis by s ...[more]

PMID: 31545475

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Project description:BackgroundThe human ether a-go-go-related gene 1 (HERG1) is involved in tumor progression; however, its role in esophageal squamous cell carcinoma (ESCC) is not well studied. This study investigated HERG1 function in ESCC progression and elucidated the underlying mechanisms.MethodsThe prognostic value of HERG1 was determined by immunohistochemistry in ESCC biopsies. Cell growth and proliferation were analyzed by colony formation and methyl thiazolyl tetrazolium assays. Cell migration and invasion were analyzed by wound healing and Boyden transwell assays. Epithelial-mesenchymal transition (EMT) was evaluated by immunoblotting and quantitative polymerase chain reaction (qPCR). A xenograft mouse model was used to validate the tumorigenic and metastatic roles of HERG1 in vivo.ResultsHERG1 expression was overall higher in ESCC tissues compared to adjacent non-tumor tissues. A retrospective analysis of 349 patients with ESCC (stages I-IV) confirmed increased HERG1 expression was associated with disease progression and higher mortality rate. The overall survival of the patients was significantly worse when their tumors displayed higher HERG1 expression. HERG1 knockdown reduced tumor growth and metastasis in athymic mice. HERG1 affected the proliferation, migration, and invasion of two ESCC cell lines (TE-1 and KYSE-30). Changes in HERG1 expression affected the expression of cell cycle- and EMT-related proteins; these effects were reversed by altering the expression of thioredoxin domain-containing protein 5 (TXNDC5), which is also associated with the clinicopathological characteristics of patients with ESCC and is relevant to HERG1 in pathological biopsies. Additionally, HERG1 expression altered phosphoinositide 3-kinase (PI3K) and AKT phosphorylation, thereby affecting TXNDC5 expression.ConclusionsHERG1 contributes to poor prognosis in patients with ESCC by promoting ESCC cell proliferation, migration, and invasion via TXNDC5 through the PI3K/AKT signaling pathway. Our findings provided novel insights into the pathology of ESCC and role of HERG1 in tumor progression, suggesting that targeting HERG1 has potential diagnostic and therapeutic value for ESCC treatment.

Dataset Information

Rap1A promotes esophageal squamous cell carcinoma metastasis through the AKT signaling pathway.

Publications

Rap1A promotes esophageal squamous cell carcinoma metastasis through the AKT signaling pathway.

Similar Datasets

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