Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression

He, Feng; Chen, Huacui; Yang, Ping; Wu, Qianlong; Zhang, Tong; Wang, Chengxing; Wei, Jianchang; Chen, Zhuanpeng; He, Hong; Li, Wanglin; Cao, Jie

doi:10.18632/oncotarget.13215

Cited by 34 publications

(30 citation statements)

References 52 publications

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“…Statistical analysis of the numbers of protein nodes revealed that proteins involved in the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway (AKT1, TP53, and PI3K family members) were significantly represented in the PPI network core (Figure 4D and 4E ). Constitutive activation of PI3K/AKT signalling promotes the proliferation of various cancers, including pancreatic cancer, while inactivation of this pathway suppresses tumour proliferation, migration, and invasion [ 16 , 17 ]. Reduced PTEN expression indirectly stimulates PI3K-AKT-mTOR activity, thereby contributing to oncogenesis in humans [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN phosphorylation

Wu³

et al. 2017

Oncotarget

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Phosphorylation is a recently established cause of phosphatase and tensin homolog (PTEN) gene inactivation, which leads to defect tumour-suppressor function. In pancreatic cancer, this phenomenon has not been reported. Based on database and clinical sample analyses, we found that PTEN phosphorylation occurs in pancreatic ductal adenocarcinoma patient tissues and cell lines, and we aimed to find a method for dephosphorylation. PDZ-containing 1 (PDZK1), a tumour-associated protein that shares its PDZ-binding sequence with the carboxyl-terminal domain of PTEN, was significantly down-regulated in pancreatic cancer as compared to adjacent non-tumour tissues. In vitro, PDZK1 overexpression reversed the proliferation and migration abilities of pancreatic cancer cells and led to significantly decreased PTEN phosphorylation and AKT phosphorylation by interacting with wild-type PTEN. In addition, a transcription factor-activation assay supported that PDZK1 overexpression enhanced the anti-oncogene function of PTEN by regulating the activities of its downstream transcription factors, including p53, NF-κB, and FOXO1. In vivo, nude mice stably over-expressing PDZK1 had lower tumour weights and volumes and showed significantly down-regulated PTEN phosphorylation in xenograft tumour tissues as compared to the control group. Moreover, low PDZK1 expression strongly correlated with advanced stage and poor prognosis of patients with pancreatic ductal adenocarcinoma. In conclusion, our study elucidated the tumour-suppressor role of PDZK1 in pancreatic cancer through down-regulating PTEN phosphorylation, and established PDZK1 as a potential novel prognostic marker for pancreatic cancer.

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Section: Resultsmentioning

confidence: 99%

PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN phosphorylation

Wu³

et al. 2017

Oncotarget

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“…Furthermore, the present study demonstrated that inhibition of PSMD10 decreased PTC cell proliferation, migration and invasion. PSMD10 is a regulator of colorectal cancer by phosphoinositide 3-kinase (PI3K)/GSK-3β/β-catenin pathway activation ( 36 ). The present study demonstrated that PSMD10 downregulation repressed GSK-3β/β-catenin and AKT signaling in PTC cells.…”

Section: Discussionmentioning

confidence: 99%

miR-214 regulates papillary thyroid carcinoma cell�proliferation and metastasis by targeting PSMD10

et al. 2018

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MicroRNAs (miRNAs) have important effects on cancer occurrence and development by adjusting gene expression. The aim of the present study was to examine the role of miR-214 in papillary thyroid carcinoma cell proliferation and metastasis, and its molecular mechanisms. miR-214 was demonstrated to be markedly downregulated in papillary thyroid carcinoma tissues and cells compared with normal, and this was significantly associated with lymph node metastasis, tumor size and TNM stage. Upregulation of miR-214 significantly decreased cell proliferation, and promoted cell apoptosis and cell cycle arrest in papillary thyroid carcinoma cell lines in vitro. By contrast, downregulation of miR-214 resulted in the opposite effects. In addition, miR-214 mimics significantly decreased papillary thyroid carcinoma cell migration and invasion, which was correlated with decreased expression levels of matrix metallopeptidase (MMP)-2 and MMP-9. Restoration of miR-214 expression in papillary thyroid carcinoma cells decreased the activities associated with epithelial-mesenchymal transition (EMT). Furthermore, proteasome 26S subunit non-ATPase 10 (PSMD10) was predicted to be a target of miR-214. Experimental results demonstrated that miR-214 negatively regulated PSMD10 expression by targeting its 3′ untranslated region directly. Knockdown of PSMD10 reduced papillary thyroid carcinoma cell clone formation, migration and invasion, most likely by repressing glycogen synthase kinase (GSK)-3β/β-catenin and AKT signaling. Finally, a negative correlation was observed between the expression levels of miR-214 and PSMD10 in papillary thyroid carcinoma tissues. Taken together, these data suggested that miR-214 might be a candidate target for the treatment of papillary thyroid carcinoma.

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“…The activation of PI3K could be triggered by oncogenes, consequently resulting in the development of tumor (18). Akt is a downstream molecule of PI3K, which is associated with cell growth and EMT, and activated Akt could promote the migration, invasion and EMT of cancer cells such as osteosarcoma cells (19)(20)(21). Therefore, inactivation of PI3K/Akt signaling could be a putative therapeutic strategy for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

“…PI3K can be activated by oncogenes, consequently activated PI3K is capable of promoting the growth and metastasis of tumor cells (18). Akt is a downstream molecule of PI3K, and it is associated with numerous biological processes, such as cell proliferation, invasion and EMT (19). The activation of Akt could induce the migration, invasion and EMT of cancer cells (20).…”

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confidence: 99%

Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

wang

liu

2020

Preprint

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Background: The expression of circRNA_100269 in gastric cancer (GC) tissues and cells, together with its regulatory roles on GC cells were investigated. Methods: The levels of circRNA_100269 in GC and matched para-carcinoma tissues, as well as in human GC cell lines and normal gastric epithelial cells were evaluated using RT-qPCR. The models with overexpression or knockdown of circRNA_100269 were generated using lentiviral vectors. Cell viability was examined using MTT assay; cell migration and invasive activity were determined by wound healing and Transwell assay. Cell cycle arrest and apoptosis were assessed; molecules involved in PI3K/Akt signaling, apoptosis and EMT were evaluated using RT-qPCR and immunoblotting. Tumour growth and expression of relevant proteins were examined in circRNA_100269 knockout mice. Results: The results indicated the expression of circRNA_100269 was dramatically decreased in GC samples compared with para-carcinoma tissues (p<0.05), while the levels of PI3K were notably increased (p<0.05). Moreover, the level of circRNA_100269 was relevant to histology grade and occurrence of metastasis in GC patients (p<0.05), where circRNA_100269 and PI3K was inversely correlated (p<0.05). Additionally, circRNA_100269 was downregulated in GC cells compared with normal gastric epithelial cells. Overexpressed circRNA_100269 remarkably suppressed the proliferation, migration, invasion and EMT of GC cells (p<0.05), induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis (p<0.05). In addition, PI3K/Akt signaling was involved in circRNA_100269-mediated proliferation, migration, invasion, EMT and apoptosis in GC cells (p<0.05). Knockdown of circRNA_100269 also significantly promoted tumor growth in vivo (p<0.05). Conclusions: the data of the present study suggested that the expression level of circRNA_100269 was decreased in GC tissues and cells. In addition, circRNA_100269 inhibited the progression of GC by suppressing PI3K/Akt signaling. Therefore, circRNA_100269/PI3K/Akt axis may be a potential therapeutic target for GC treatment.

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Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression

Cited by 34 publications

References 52 publications

PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN phosphorylation

PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN phosphorylation

miR-214 regulates papillary thyroid carcinoma cell�proliferation and metastasis by targeting PSMD10

Upregulated circRNA_100269 suppresses the growth and metastasis of gastric cancer by inactivating PI3K/Akt signaling pathway

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