Interaction with CCNH/CDK7 facilitates CtBP2 promoting esophageal squamous cell carcinoma (ESCC) metastasis via upregulating epithelial-mesenchymal transition (EMT) progression

Zhang, Jianguo; Zhu, Junya; Yang, Lei; Guan, Chengqi; Ni, Runzhou; Wang, Yuchan; Ji, Lili; Tian, Ye

doi:10.1007/s13277-015-3354-x

Cited by 24 publications

(18 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CDK7 was significantly (p < 0.05) negatively correlated with the expression of mesenchymal markers including FN1, VIM and MMP2. Role of CDK7 on cancer metastasis has been reported by one group that CCNH/CDK7 can interact with CtBP2 to promote cell migration of breast cancer [29] and esophageal squamous cell carcinoma [30]. In agreement with our findings, recent studies suggested that CDKs controlled the migration and metastatic potential of cancer cells [31].…”

Section: Discussionsupporting

confidence: 93%

Targeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer

Zhou

Jiang

et al. 2018

Cell Death Differ

View full text Add to dashboard Cite

Targeted inhibition of cyclin-dependent kinase 7 (CDK7) via its covalent inhibitor THZ1 can suppress the growth of various cancers, while its roles on colorectal cancer (CRC) remain obscure. Here we report that the expression of CDK7 is upregulated in CRC cells and tissues. THZ1 exhibits high potency and selectivity against CRC cells both in vitro and in vivo via induction of cell apoptosis rather than cell cycle disruption. Intriguingly, THZ1 treatment increases the ability of epithelial mesenchymal transition (EMT) and in vivo metastasis to liver of CRC cells. Mechanistical studies reveal that THZ1 increases the expression of Snail, while not other EMT-transcription factors, via enhancing its protein stability rather than mRNA expression or translation. By screening Snail stability related factors via qRT-PCR, results indicate THZ1 and si-CDK7 decrease the expression of protein kinase D1 (PKD1) in CRC cells. Down regulation of PKD1 mediates THZ1 up regulated Snail via dephosphorylation of Snail Ser 11 and prevention of proteasome mediated degradation. Clinical analysis confirms that CDK7 is significantly (p < 0.05) negatively correlated with the expression of mesenchymal markers including FN1, VIM, and MMP2. CRC patients whose tumors expressing less CDK7/SNAI1 or PKD1/SNAI1 showed significant (p < 0.05) poorer overall survival (OS) rate as compared with those with greater levels. Collectively, our data suggest that targeted inhibition of CDK7 can trigger the metastasis of CRC during cancer development via PKD1/Snail axis, which imposes great challenge that inhibition of CDK7 is a potential approach for cancer treatment.

show abstract

Section: Discussionsupporting

confidence: 93%

Targeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer

Zhou

Jiang

et al. 2018

Cell Death Differ

View full text Add to dashboard Cite

show abstract

“…A549 cells were seeded in 6-well plates (Corning, Inc.) and transfected with NLK-shRNA, control-shRNA and full-length NLK according to the manufacturer's instructions (19). When they reached ~80% confluency 48 h post-transfection, cells were serum-starved for 12 h, then scratched using the fine end of a 100-µl pipette tip.…”

Section: Methodsmentioning

confidence: 99%

Knockdown of Nemo‑like kinase promotes metastasis in non‑small‑cell lung cancer

Shi

Tang

et al. 2019

Oncol Rep

View full text Add to dashboard Cite

The evolutionarily conserved serine/threonine kinase Nemo-like kinase (NLK) serves an important role in cell proliferation, migration, invasion and apoptosis by regulating transcription factors among various cancers. In the present study, the function of NLK in human non-small cell lung cancer (NSCLC) was investigated. Immunohistochemical analysis and western blotting demonstrated that NLK expression was significantly reduced in NSCLC tissues compared with corresponding peritumoral tissues. Statistical analysis revealed that decreased NLK expression was associated with the presence of primary tumors, tumor node metastasis (TNM) staging, differentiation, lymph node metastasis, and E-cadherin and vimentin expression. Univariate analysis indicated that NLK expression, differentiation, lymph node metastasis, TNM stage, and E-cadherin and vimentin expression affected the prognosis of NSCLC. Cox regression analyses revealed NLK expression and TNM as independent factors that affected prognosis. Kaplan-Meier survival analysis revealed that patients with NSCLC and low NLK expression had relatively shorter durations of overall survival. In vitro , NLK overexpression inhibited A549 ncell migration and invasion as determined by wound healing and Transwell migration assays, respectively. Additionally, immunofluorescence staining indicated that downregulation of NLK expression could induce epithelial-mesenchymal transition in NSCLC. NLK knockdown significantly decreased the expression of the epithelial marker E-cadherin, and markedly increased that of β-catenin and the mesenchymal marker vimentin. Furthermore, NLK was reported to directly interact with β-catenin as determined by a co-immunoprecipitation assay. Collectively, the results of the present study indicated that decreased NLK expression could promote tumor metastasis in NSCLC.

show abstract

“…expression of CtBP2 was upregulated in ESCC tissues (27,28). In addition, CtBP2 predicts a poor prognosis in human cancers, including ESCC (27).…”

Section: C-terminal Binding Protein-2 Mediates Cisplatin Chemoresistamentioning

confidence: 95%

C-terminal binding protein‑2 mediates cisplatin chemoresistance in esophageal cancer cells via the inhibition of apoptosis

Shi

Mao

et al. 2018

Int J Oncol

View full text Add to dashboard Cite

C-terminal binding protein‑2 (CtBP2) is a transcriptional co-repressor that is associated with tumorigenesis and tumor progression. It has been reported to predict a poor prognosis in several human cancers, including esophageal squamous cell carcinoma (ESCC). The present study aimed to investigate the involvement of CtBP2 in the cisplatin (DDP) resistance of the ECA109 ESCC cell line and its effect on the expression of apoptosis-associated proteins. Constructed recombinant lentiviruses were used for the knockdown or overexpression of CtBP2 in ECA109 cells, and the expression of CtBP2 was measured using reverse transcription-quantitative polymerase chain reaction and western blotting following transfection. MTT assays, Hoechst 33342 staining and flow cytometry (FCM) were applied to detect the influence of CtBP2 on the DDP-induced viability and apoptosis of the transfected ECA109 cells. In addition, the levels of apoptosis-associated proteins, including p53, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and activated caspase-3 were investigated in the transfected ECA109 cells. Stable ECA109 cells with CtBP2 overexpression or knockdown were successfully established. The results of the MTT, Hoechst 33342 and FCM assays demonstrated that overexpression of CtBP2 attenuated the reduction of cell viability and inhibited the cell apoptosis induced by DDP. Furthermore, the western blotting results indicated that CtBP2 overexpression inhibited the DDP-induced apoptosis of ECA109 cells via the reduction of p53, activated caspase-3 and Bax expression, and promotion of Bcl‑2 expression. Therefore, the present study indicated that CtBP2 reduced the susceptibility of ECA109 cells to DDP by regulating the expression of apoptosis-related proteins, suggesting that it may be a promising therapeutic target in ESCC in the future.

show abstract

Interaction with CCNH/CDK7 facilitates CtBP2 promoting esophageal squamous cell carcinoma (ESCC) metastasis via upregulating epithelial-mesenchymal transition (EMT) progression

Cited by 24 publications

References 35 publications

Targeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer

Targeting CDK7 increases the stability of Snail to promote the dissemination of colorectal cancer

Knockdown of Nemo‑like kinase promotes metastasis in non‑small‑cell lung cancer

C-terminal binding protein‑2 mediates cisplatin chemoresistance in esophageal cancer cells via the inhibition of apoptosis

Contact Info

Product

Resources

About