Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

Background/Aims: Slug protein, a transcription factor for the induction of epithelial-mesenchymal transition (EMT) and cancer cell invasion and metastasis, is frequently upregulated in human epithelial cancers. However, mutation of this gene in cancer is rare, and the mechanism of its dysregulation remains unknown, especially in head and neck squamous cell carcinoma (HNSCC). Methods: We examined the role of TNF-α in the stabilization of Slug by immunoprecipitation-westernblot analysis. Migration of HNSCC cells with or without knockdown of Slug gene expression was assayed by a wound healing assay. Immunohistochemical staining analysis was used to measurement Slug levels in both normal and HNSCC tumor tissues. Results: The inflammatory cytokine TNF-α stabilized Slug protein by inhibiting its ubiquitination through the NF-κB pathway. Inhibition of NF-κB or knockdown of p65 abrogated the TNF-α-induced stabilization of Slug. Knockdown of Slug expression inhibited cancer cell migration and EMT characteristics induced by TNF-α. Moreover, increased levels of Slug were found to correlate with lymph node metastasis and predict poor prognosis in patients with HNSCC. Conclusions: NF-κB-mediated stabilization of Slug underlies the inflammation-induced EMT and metastasis in HNSCC, which may serve as a therapeutic target for metastatic HNSCC.

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“…Experiment protocol was performed as described previously [25,26]. Cells were lysed with RIPA lysis buffer.…”

Section: Immunoprecipitation and Western Blottingmentioning

confidence: 99%

Stabilization of Slug by NF-κB is Essential for TNF-α -Induced Migration and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cells

Liu

Shi

Wang

et al. 2018

Cell Physiol Biochem

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“…As numerous genetic changes are in relation to cancer cell invasion and metastasis,14, 19, 20, 21, 22 great efforts have been made in the identification of novel key regulators and the potential mechanisms involved in this process over the years. Interestingly, recent studies have revealed that CRYAB is aberrantly overexpressed in various types of cancer, and its expression could promote cell invasion and metastasis 8, 9, 10.…”

Section: Discussionmentioning

confidence: 99%

“…As numerous genetic changes are in relation to cancer cell invasion and metastasis, 14,[19][20][21][22] possibly by targeting CRYAB-mediated cell motility. 9 Obviously, these findings provide evidence delineating the pivotal role of CRYAB in cancer invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

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Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition

Chen

Cao

Qiao

et al. 2018

J Cellular Molecular Medi

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Alpha B‐crystallin (CRYAB) is overexpressed in a variety of cancers. However, little is known about its specific function and regulatory mechanism in gastric cancer. Here, we first explore the role of CRYAB in gastric cancer progression and metastasis. The expression of CRYAB was determined by western blot and immunohistochemistry in gastric cancer tissues. Besides, methods including stably transfected against CRYAB into gastric cancer cells, western blot, migration and invasion assays in vitro and metastasis assay in vivo were also conducted. The expression of CRYAB is up‐regulated in gastric cancer tissues compared with matched normal tissues. High expression level of CRYAB is closely correlated with cancer metastasis and shorter survival time in patients with gastric cancer. Additionally, CRYAB silencing significantly suppresses epithelial‐mesenchymal transition (EMT), migration and invasion of gastric cancer cells in vitro and in vivo, whereas CRYAB overexpression dramatically reverses these events. Mechanically, CRYAB facilitates gastric cancer cells invasion and metastasis via nuclear factor‐κ‐gene binding (NF‐κB)‐regulated EMT. These findings suggest that CRYAB expression predicts a poor prognosis in patients with gastric cancer. Besides, CRYAB contributes to gastric cancer cells migration and invasion via EMT, mediated by the NF‐κB signalling pathway, thus possibly providing a novel therapeutic target for gastric cancer.

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“…Cheng et al found that the Akt pathway was involved in mTOR/p70S6k signaling pathway, which is crucial in epithelial mesenchymal transformation (EMT) 31 . Furthermore, Chen et al also provided an evidence of ARK5 involvement in Akt/mTOR/p70S6k signaling pathway, which induced invasion and metastasis of gastric cancer 32 .…”

Section: Role Of Ark5 In Pi3k/akt Pathwaymentioning

confidence: 96%

Deciphering the role of AMPK-related kinase 5 in human cancer progression and metastasis

2019

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Malignancies related mortality is currently growing at an alarming rate. Early detection of cancer is vital in order to improve survival rates of cancer patients, and biomarker detection is regarded as one of the most promising approaches. Recent studies have reported that elevated ARK5 expression is associated with tumor progression and metastasis in several human malignancies. Several pathways are also influenced by the presence of ARK5, most notably the PI3k-Akt pathway, m-TOR phosphorylation, and several pathways that induce increased tumor invasion activity. Additionally, ARK5 expression are linked to miR-1181 down-regulation, which promotes epithelial mesenchymal transformation in ovarian cancer cells. Furthermore, ARK5 gene transcription is also affected by the interaction of c-MAF and MAFB with both MARE core sequences present in the ARK5 promoter. Based on the current evidences, ARK5 might be the master regulator of cancer progression and metastasis, which could potentially serve as a novel target for cancer therapies.

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Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

Cited by 37 publications

References 35 publications

Stabilization of Slug by NF-κB is Essential for TNF-α -Induced Migration and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cells

Stabilization of Slug by NF-κB is Essential for TNF-α -Induced Migration and Epithelial-Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma Cells

Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition

Deciphering the role of AMPK-related kinase 5 in human cancer progression and metastasis

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