Dataset Information

TIP-B1 promotes kidney clear cell carcinoma growth and metastasis via EGFR/AKT signaling.

ABSTRACT: Kidney clear cell carcinoma (KIRC) is the most prevalent kidney malignancy. Accumulating evidence shows that high expression of TIP-B1 correlates with development of tumor progression. However, the detailed functions of TIP-B1 in the KIRC remain to be further elucidated. Here, we firstly found TIP-B1 expression was significantly increased in KIRC compared with adjacent normal tissues. What's more, higher expression of TIP-B1 were correlated with aggressive clinico-pathological characteristics. In vitro assay found TIP-B1 knockdown dramatically inhibited KIRC cells proliferation, migration and invasion. In vivo assay found down regulated TIP-B1 could suppress tumor growth and metastasis. Mechanism analysis indicated that TIP-B1 could bind EGFR and suppress EGFR degradation, then promoted EGF-induced AKT signaling. Together, TIP-B1 could be applied as an independent risk factor to predict KIRC progression and metastasis. Targeting TIP-B1 might be a new potential therapeutic strategy for KIRC treatment.

SUBMITTER: Yin L

PROVIDER: S-EPMC6782011 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TIP-B1 promotes kidney clear cell carcinoma growth and metastasis via EGFR/AKT signaling.

Yin Lei L Gao Shenglin S Shi Heng H Wang Keyi K Yang Huan H Peng Bo B

Aging 20190927 18

Kidney clear cell carcinoma (KIRC) is the most prevalent kidney malignancy. Accumulating evidence shows that high expression of TIP-B1 correlates with development of tumor progression. However, the detailed functions of TIP-B1 in the KIRC remain to be further elucidated. Here, we firstly found TIP-B1 expression was significantly increased in KIRC compared with adjacent normal tissues. What's more, higher expression of TIP-B1 were correlated with aggressive clinico-pathological characteristics. I ...[more]

PMID: 31562290

Similar Datasets

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.

Project description:BackgroundHepatocellular carcinoma is the third top cause of cancer-related mortalities worldwide. The prognosis of HCC patients remains poor due to rapid progression and high incidence of tumor recurrence. Nicastrin (NCSTN), a core subunit of γ-Secretase, has been reported to play a vital role in tumor progression. However, no study till now has revealed its role in HCC.MethodsThe expression of NCSTN was evaluated by immunohistochemical staining, Western blot, and quantitative real-time PCR. Cell counting kit-8, colony formation and cell cycle assays were used for evaluating cell growth in vitro. Transwell and wound-healing assays were used for evaluating cell migration and invasion capacity. Immunofluorescence, subcellular protein fractionation and co-immunoprecipitation were used for location analysis of β-catenin. The in vivo functions of NCSTN were illustrated by xenograft tumor models.ResultsNCSTN was dramatically overexpressed in HCC compared to normal liver tissues. Elevated NCSTN expression level was significantly correlated to worse overall and recurrence-free survival of HCC patients. Enhanced NCSTN expression promoted HCC cell growth, migration and invasion in vitro and in vivo. Mechanistic investigations showed that NCSTN induced epithelial-mesenchymal transition (EMT) process via upregulation of Zeb1. Subsequently, we revealed that NCSTN facilitated nuclear translocation of β-catenin, a positive transcriptional regulator of Zeb1. Using Notch and AKT inhibitors, we revealed that NCSTN promoted β-catenin activation through Notch1 and AKT signaling pathway. NCSTN increased AKT and GSK-3β phosphorylation by cleavage of Notch1, which decreased GSK-3β/β-catenin complex. The inactivation of GSK-3β inhibited the β-catenin degradation and promoted nuclear translocation of β-catenin to initiate transcription of Zeb1, resulting in malignant phenotype.ConclusionsOur results demonstrated that NCSTN promoted HCC cell growth and metastasis via β-catenin-mediated upregulation of Zeb1 in a Notch1/AKT dependent manner, suggesting that NCSTN might serve as a potential prognostic marker and therapeutic target for HCC.

Dataset Information

TIP-B1 promotes kidney clear cell carcinoma growth and metastasis via EGFR/AKT signaling.

Publications

TIP-B1 promotes kidney clear cell carcinoma growth and metastasis via EGFR/AKT signaling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets