Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells

Li, Quanying; Tang, Hongna; Hu, Fangfang; Qin, Changjiang

doi:10.1002/jcb.27331

Cited by 3 publications

(4 citation statements)

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“…The acquisition of an EMT phenotype is a critical process for switching early stage carcinomas into invasive malignancies, which is often associated with the loss of epithelial differentiation and gain of mesenchymal phenotype [20, 23]. We next examined the morphologic features of GC cells.…”

Section: Resultsmentioning

confidence: 99%

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Ubiquitin-specific protease 3 promotes cell migration and invasion by interacting with and deubiquitinating SUZ12 in gastric cancer

Liu

Zhu

et al. 2019

J Exp Clin Cancer Res

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Background The deubiquitinating enzyme ubiquitin-specific protease 3 (USP3) plays a crucial role in numerous biological processes. The aberrant expression of USP3 may have an important role in tumor development. However, the mechanism by which USP3 promotes gastric cancer (GC) metastasis remains largely unknown. Methods Effects of USP3 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated utilizing proteomics, RT-PCR, western blotting, immunohistochemistry, immunofluorescence, cell invasion and migration assays and xenograft tumor models. Results USP3 expression was upregulated in GC compared with matched normal tissues and was predictive of poor survival. USP3 also promoted migration and epithelial-to-mesenchymal transition (EMT) in GC cells. Moreover, TGF-β1 induced USP3 expression, and USP3 knockdown inhibited TGF-β1-induced EMT. Furthermore, we utilized Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) to identify differentially expressed proteins in USP3-overexpressing cells compared with control cells. Importantly, we found that SUZ12 is indispensable for USP3-mediated oncogenic activity in GC. We observed that USP3 interacted with and stabilized SUZ12 via deubiquitination. SUZ12 knockdown inhibited USP3-induced migration and invasion, as well as EMT in GC cells. Examination of clinical samples confirmed that USP3 expression was positively correlated with SUZ12 protein expression and that the levels of USP3 or SUZ12 protein were negatively correlated with the levels of E-cadherin protein. Conclusions These findings identify USP3 as a critical regulator. The USP3-SUZ12 axis might promote tumor progression and could be a potential therapeutic candidate for human GC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1270-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

“…EMT is implicated in the initial step of cancer metastasis and is indispensable for cancer cells to break through the barriers formed by normal tissues so that a tumor can metastasize [20, 23, 27]. The heterogeneity in GC also increases the risk of gastric carcinoma progression and metastasis and exacerbates therapeutic resistance [28].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific protease 3 promotes cell migration and invasion by interacting with and deubiquitinating SUZ12 in gastric cancer

Liu

Zhu

et al. 2019

J Exp Clin Cancer Res

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“…Hypoxia is a characteristic of tumor microenvironments. [15][16][17] In response to hypoxia, HIF-1α is stabilized. MCU silencing can down-regulate the expression of HIF-1α, thereby attenuating the transcription of HIF-1α target genes related to the progression of TNBC.…”

Section: Discussionmentioning

confidence: 99%

<p>The Regulatory Mechanism and Biological Significance of Mitochondrial Calcium Uniporter in the Migration, Invasion, Angiogenesis and Growth of Gastric Cancer</p>

Wang

Song

Cheng

et al. 2020

OTT

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“…Western blotting was performed as described previously [23]. Total proteins were extracted with radioimmunoprecipitation assay (RIPA) buffer supplemented with 1% phenylmethanesulfonyl fluoride (PMSF).…”

Section: Western Blottingmentioning

confidence: 99%

KIF20A Predicts Poor Survival of Patients and Promotes Colorectal Cancer Tumor Progression through the JAK/STAT3 Signaling Pathway

Zhang¹,

Di²,

et al. 2020

Disease Markers

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Kinesin family member 20A (KIF20A) has been recently reported to be upregulated and associated with increased invasiveness and metastasis in several malignancies. However, the role of KIF20A in colorectal cancer (CRC) is still unclear. This study is aimed at investigating the potential roles of KIF20A in the development of CRC. The results of bioinformatics analysis, immunohistochemical staining, and Western blot analysis showed that KIF20A was overexpressed in CRC tissues compared with adjacent normal tissues. High expression of KIF20A in CRC tissues was associated with depth of invasion, lymphatic node metastasis, distant metastasis, and TNM stage. Moreover, the Kaplan-Meier survival analysis showed that CRC patients with high KIF20A expression had poor prognoses. Cox regression analysis revealed that KIF20A was an independent prognostic factor in patients with CRC. Further studies suggested that knockdown of KIF20A was able to reduce cell proliferation and migration by inhibiting the JAK/STAT3 pathway. Taken together, we propose that KIF20A plays a critical role in the tumorigenesis and tumor progression of colorectal cancer and could represent a potential therapeutic target for CRC.

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Knockdown of A‐kinase anchor protein 4 inhibits hypoxia‐induced epithelial‐to‐mesenchymal transition via suppression of the Wnt/β‐catenin pathway in human gastric cancer cells

Cited by 3 publications

References 28 publications

Ubiquitin-specific protease 3 promotes cell migration and invasion by interacting with and deubiquitinating SUZ12 in gastric cancer

Ubiquitin-specific protease 3 promotes cell migration and invasion by interacting with and deubiquitinating SUZ12 in gastric cancer

<p>The Regulatory Mechanism and Biological Significance of Mitochondrial Calcium Uniporter in the Migration, Invasion, Angiogenesis and Growth of Gastric Cancer</p>

KIF20A Predicts Poor Survival of Patients and Promotes Colorectal Cancer Tumor Progression through the JAK/STAT3 Signaling Pathway

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