Tankyrases/β-catenin Signaling Pathway as an Anti-proliferation and Anti-metastatic Target in Hepatocarcinoma Cell Lines

Huang, Jianghai; Qu, Qiang; Guo, Yong; Xiang, Yuqi; Feng, Daxiong

doi:10.7150/jca.30976

Cited by 26 publications

(22 citation statements)

References 37 publications

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“…demonstrated that TNKS knockdown can inhibit the proliferation, invasion and epithelial-to-mesenchymal transition (EMT) process in hepatocellular carcinoma cells (11). However, the underlying molecular mechanisms of TNKS in gastric cancer remain unclear.…”

Section: Dihydroartemisinin Suppresses Proliferation Migration the Wnt/β-catenin Pathway And Emt Via Tnks In Gastric Cancermentioning

confidence: 99%

Dihydroartemisinin suppresses proliferation, migration, the Wnt/β‑catenin pathway and EMT via TNKS in gastric cancer

Zhang

et al. 2021

Oncol Lett

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Gastric cancer is a common malignancy worldwide. However, the molecular mechanisms underlying this malignancy remain unclear and there are a lack of effective drugs. The present study aimed to investigate the antitumor effect of Dihydroartemisinin (DHA) or inhibition of Tankyrases (TNKS), and determine the underlying molecular mechanisms of gastric cancer. Immunohistochemistry and immunofluorescence analyses were performed to detect the expression levels of TNKS, epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin pathway-related proteins in gastric cancer tissues and adjacent normal tissues. The Cell Counting Kit-8 assay was performed to assess the viability of HGC-27 and AGS cells following treatment with different concentrations of HLY78 (a Wnt activator) or DHA. Following treatment with HLY78, DHA or small interfering (si)-TNKS1/si-TNKS2, colony formation and migratory abilities were assessed via the colony formation, wound healing and Transwell assays. Furthermore, western blot and immunofluorescence analyses were performed to detect the expression levels of TNKS, EMT-and Wnt/β-catenin-related proteins. The results demonstrated that the expression levels of TNKS, AXI2, β-catenin, N-cadherin and Vimentin were upregulated, whereas E-cadherin expression was downregulated in gastric cancer tissues compared with normal tissues. Furthermore, HLY78 and DHA suppressed the viability of HGC-27 and AGS cells, in a concentration-independent manner. Notably, TNKS knockdown or treatment with DHA suppressed colony formation, migration, TNKS expression, EMT and the Wnt/β-catenin pathway. Opposing effects were observed following treatment with HLY78, which were ameliorated following co-treatment with DHA. Taken together, these results suggest that DHA or inhibition of TNKS can suppress the proliferation and migration of gastric cancer cells, which is partly associated with inactivation of the Wnt/β-catenin pathway and EMT process.

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Section: Dihydroartemisinin Suppresses Proliferation Migration the Wnt/β-catenin Pathway And Emt Via Tnks In Gastric Cancermentioning

confidence: 99%

Dihydroartemisinin suppresses proliferation, migration, the Wnt/β‑catenin pathway and EMT via TNKS in gastric cancer

Zhang

et al. 2021

Oncol Lett

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“…TNKS were previously implicated in the regulation of cell migration. Since TNKS are overall overexpressed in several cancer types and are promising targets to block the Wnt pathway in particular, the pharmacological inhibition of TNKS or their siRNA-mediated depletion was tested and shown in numerous studies to decrease the migration and invasion of cancer cell lines [34][35][36][37][38][39][40][41]. Given the plethora of TNKS partners, the mechanisms at play may not be the same in all cell systems.…”

Section: Discussionmentioning

confidence: 99%

Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex

Simanov

Dang

Fokin

et al. 2021

IJMS

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During cell migration, protrusion of the leading edge is driven by the polymerization of Arp2/3-dependent branched actin networks. Migration persistence is negatively regulated by the Arp2/3 inhibitory protein Arpin. To better understand Arpin regulation in the cell, we looked for its interacting partners and identified both Tankyrase 1 and 2 (TNKS) using a yeast two-hybrid screening and coimmunoprecipitation with full-length Arpin as bait. Arpin interacts with ankyrin repeats of TNKS through a C-terminal-binding site on its acidic tail, which overlaps with the Arp2/3-binding site. Arpin was found to dissolve the liquid–liquid phase separation of TNKS upon overexpression. To uncouple the interactions of Arpin with TNKS and Arp2/3, we introduced point mutations in the Arpin tail and attempted to rescue the increased migration persistence of the Arpin knockout cells using random plasmid integration or compensating knock-ins at the ARPIN locus. Arpin mutations impairing interactions with either Arp2/3 or TNKS were insufficient to fully abolish Arpin activity. Only the mutation that affected both interactions rendered Arpin completely inactive, suggesting the existence of two independent pathways, whereby Arpin controls the migration persistence.

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“…Wnt inhibitors inhibit the Wnt/β-catenin pathway and cancer cell growth through the impairment of β-catenin stabilization [44,53,54]. Since clinical data show that elevated Wnt signaling correlates with a worse outcome for a subset of human cancers, a number of inhibitors targeting the Wnt pathway have advanced to clinical trials [47,55].…”

Section: Discussionmentioning

confidence: 99%

Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma

Raineri

Bourgoin-Voillard

Cossutta

et al. 2021

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and resistant cancer with no available effective therapy. We have previously demonstrated that nucleolin targeting by N6L impairs tumor growth and normalizes tumor vessels in PDAC mouse models. Here, we investigated new pathways that are regulated by nucleolin in PDAC. We found that N6L and nucleolin interact with β-catenin. We found that the Wnt/β-catenin pathway is activated in PDAC and is necessary for tumor-derived 3D growth. N6L and nucleolin loss of function induced by siRNA inhibited Wnt pathway activation by preventing β-catenin stabilization in PDAC cells. N6L also inhibited the growth and the activation of the Wnt/β-catenin pathway in vivo in mice and in 3D cultures derived from MIA PaCa2 tumors. On the other hand, nucleolin overexpression increased β-catenin stabilization. In conclusion, in this study, we identified β-catenin as a new nucleolin interactor and suggest that the Wnt/β-catenin pathway could be a new target of the nucleolin antagonist N6L in PDAC.

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Tankyrases/β-catenin Signaling Pathway as an Anti-proliferation and Anti-metastatic Target in Hepatocarcinoma Cell Lines

Cited by 26 publications

References 37 publications

Dihydroartemisinin suppresses proliferation, migration, the Wnt/β‑catenin pathway and EMT via TNKS in gastric cancer

Dihydroartemisinin suppresses proliferation, migration, the Wnt/β‑catenin pathway and EMT via TNKS in gastric cancer

Arpin Regulates Migration Persistence by Interacting with Both Tankyrases and the Arp2/3 Complex

Nucleolin Targeting by N6L Inhibits Wnt/β-Catenin Pathway Activation in Pancreatic Ductal Adenocarcinoma

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