STK17B promotes carcinogenesis and metastasis via AKT/GSK-3β/Snail signaling in hepatocellular carcinoma

Lan, Yaliang; Han, Jianyong; Wang, Yan; Wang, Jiabei; Yang, Guangchao; Li, Keyu; Song, Ran; Zheng, Tongsen; Liang, Yingjian; Pan, Shangha; Liu, Xirui; Zhu, Mingxi; Liu, Yao; Meng, F.; Mohsin, Manzoor; Cui, Yifeng; Zhang, Bo; Subash, Sharma; Liu, Lianxin

doi:10.1038/s41419-018-0262-1

Cited by 48 publications

(47 citation statements)

References 35 publications

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“…In addition to HNSCC, DRAK1 was found to be overexpressed in several gliomas compared to normal brain or other cancer types with the highest level of overexpression in glioblastoma multiforme (GBM) and associated with decreased patient survival. Knockdown of DRAK1 in U87, SF268, U118, A172, and U563 GBM cell lines significantly decreased cellular proliferation, motility, and invasion . These findings suggest developing DRAK1 inhibitors as a potential strategy for treatment of GBM.…”

Section: Dapks Cellular Functionsmentioning

confidence: 79%

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Farag

Roh

2018

Medicinal Research Reviews

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Serine/threonine kinases (STKs) represent the majority of discovered kinases to date even though a few Food and Drug Administration approved STKs inhibitors are reported. The third millennium came with the discovery of an important group of STKs that reshaped our understanding of several biological signaling pathways. This family was named death-associated protein kinase family (DAPK family). DAPKs comprise five members (DAPK1, DAPK2, DAPK3, DRAK1, and DRAK2) and belong to the calcium/calmodulin-dependent kinases domain. As time goes on, the list of biological functions of this family is constantly updated. The most extensively studied member is DAPK1 (based on the publications number and Protein Data Bank reported crystal structures) that plays fundamental biological roles depending on the cellular context. DAPK1 regulates apoptosis, autophagy, contributes to the pathogenesis of Alzheimer's disease, acts as a tumor suppressor, inhibits metastasis, mediates the body responses to viral infections, and regulates the synaptic plasticity and depression. For their biological roles, several DAPKs' modulators have been reported for treatment of many diseases as well as acting as probe compounds to facilitate the understanding of the biological functions elicited by this family. Despite that, the number of reported modulators is still limited and more research needs to be conducted on the discovery of novel strategies to activate or inhibit this family. In this report, we aim at drawing more attention to this family by reviewing the recent updates regarding the structure, biological roles, and regulation of this family. In addition, the small-molecule modulators of this family are reviewed in details with their potential therapeutic outcomes evaluated to help medicinal chemists develop more potent and selective possible drug candidates.

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Section: Dapks Cellular Functionsmentioning

confidence: 79%

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Farag

Roh

2018

Medicinal Research Reviews

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“…The immunofluorescence (IF) assay was performed as described previously (28). Cultured cells were fixed with 4% (w/v) paraformaldehyde (Sigma) for 10 minutes, and permeabilized with 0.1% (v/v) Triton X-100 at room temperature for 20 minutes.…”

Section: Immunofluorescence Assaymentioning

confidence: 99%

“…A Luciferase Assay Kit (Promega) was accessed for luciferase activity as described previously (28). Cells were cultured in 24well plates and then incubated for 24 hours.…”

Section: Luciferase Assaymentioning

confidence: 99%

A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis

Liu

Meng

Wang

et al. 2019

Clinical Cancer Research

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Purpose: As a main rate-limiting subunit of the 2-oxoglutarate dehydrogenase multienzyme complex, oxoglutarate dehydrogenase like (OGDHL) is involved in the tricarboxylic acid cycle, and frequently downregulated in human carcinoma and suppresses tumor growth. However, little is known about the role of OGDHL in human cancer, especially pancreatic cancer. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by OGDHL modulating pancreatic cancer progression. Experimental Design: The expression and functional analysis of OGDHL, miR-214, and TWIST1 in human pancreatic cancer tissues, cell lines, and xenograft tumor model were investigated. The correlations between OGDHL and those markers were analyzed. Results: OGDHL was downregulated in human pancreatic cancer and predicted poor prognosis. OGDHL overexpression inhibited migration and invasion of pancreatic cancer cells and suppressed pancreatic cancer tumor growth. OGDHL was shown to be negatively regulated by miR-214. TWIST1 upregulation induced miR-214 expression in pancreatic cancer. OGDHL suppressed TWIST1 expression through promoting ubiquitin-mediated proteasomal degradation of HIF1a and regulating AKT pathways. A combination of OGDHL downregulation and TWIST1 and miR-214 overexpression predicted worse prognosis in patients with pancreatic cancer. Conclusions: We demonstrated the prognostic value of OGDHL, miR-214, and TWIST1 in pancreatic cancer, and elucidated a novel pathway in OGDHL-regulated inhibition of pancreatic cancer tumorigenesis and metastasis. These findings may lead to new targeted therapy for pancreatic cancer through regulating OGDHL, miR-214, and TWIST1.

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“…The AKT/GSK-3β/Snail pathway has been shown to be involved in HCC metastasis by inducing epithelial-mesenchymal transition (EMT) (16,17). The transcription factor Snail, controls EMT by repressing the expressions of E-cadherin and other epithelial genes, and GSK-3β phosphorylates Snail inducing its degradation (18).…”

Section: Bay 87-2243 Combined With Hdac Inhibitors Induces Cell Deathmentioning

confidence: 99%

BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation

Rao

Zhang

et al. 2019

Exp Ther Med

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Hepatocellular carcinoma (HCC) is associated with some of the highest cancer-associated mortality rates. Histone deacetylase (HDAC) inhibitors anti-HCC activities have been shown to promote Snail-induced metastasis. In the present study, it was shown that BAY 87-2243, a hypoxia-inducible transcription factor-1α inhibitor, could enhance the anti-HCC effects of HDAC inhibitors, including trichostatin A and vorinostat. In addition, BAY 87-2243 plus HDAC inhibitors exhibited synergistic cytotoxicity and induced significant cell death in Hep3B cells. Additionally, BAY 87-2243 combined with HDAC inhibitors-treated Hep3B cells formed fewer and smaller colonies as compared with either the control or single agent-treated cells. Furthermore, glycogen synthase kinase-3β might be involved in the enhanced cell death induced by BAY 87-2243 plus HDAC inhibitors. The present data also indicated that BAY 87-2243 combined with HDAC inhibitors could suppress the migration of Hep3B cells, and BAY 87-2243 could reverse the HDAC inhibitor-induced Snail activation in Hep3B cells. In conclusion, BAY 87-2243 combined with HDAC inhibitors might be an attractive chemotherapy strategy for HCC therapy.

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STK17B promotes carcinogenesis and metastasis via AKT/GSK-3β/Snail signaling in hepatocellular carcinoma

Cited by 48 publications

References 35 publications

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

Death‐associated protein kinase (DAPK) family modulators: Current and future therapeutic outcomes

A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis

BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation

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