Wnt/β-Catenin Signaling Regulates Yes-associated Protein (YAP) Gene Expression in Colorectal Carcinoma Cells

Konsavage, Wesley M.; Kyler, Sydney L.; Rennoll, Sherri A.; Jin, Ge; Yochum, Gregory S.

doi:10.1074/jbc.m111.327767

Cited by 245 publications

(246 citation statements)

References 43 publications

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“…miR-135b has also been reported to induce Wnt signalling pathway by the suppression of APC in colorectal cancers 16 , and the Hippo pathway has been reported to inhibit the Wnt pathway during heart development 49 . This crosstalk has also been described in cancer cells when the Hippo pathway retains b-catenin in the cytoplasm through a physical interaction between phosphorylated TAZ/YAP and b-catenin 50,51 . Our results suggest that the upregulation of miR-135b in lung cancer may antagonize the Hippo pathway and inhibit the Wnt/b-catenin pathway through direct APC and b-TrCP suppression.…”

Section: Discussionmentioning

confidence: 73%

MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1

et al. 2013

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Dysregulation of microRNAs has a critical role in cancer progression. Here we identify an intronic microRNA, miR-135b that is upregulated in highly invasive non-small-cell lung cancer cells. Expression of miR-135b enhances cancer cell invasive and migratory abilities in vitro and promotes cancer metastasis in vivo, while specific inhibition of miR-135b by a miR-135b-specific molecular sponge and antagomirs suppresses cancer cell invasion, orthotopic lung tumour growth and metastasis in a mouse model. miR-135b targets multiple key components in the Hippo pathway, including LATS2, b-TrCP and NDR2, as well as LZTS1. Expression of miR-135b, LZTS1, LATS2 and nuclear TAZ predicts poor outcomes of non-small-cell lung cancer. We find that miR-135b is dually regulated by DNA demethylation and nuclear factor-kappaB signalling, implying that abnormal expression of miR-135b in cancer may result from inflammatory and epigenetic modulations. We conclude that miR-135b is an oncogenic microRNA and a potential therapeutic target for non-small-cell lung cancer.

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Section: Discussionmentioning

confidence: 73%

MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1

et al. 2013

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“…Our results showed that Tau could induce apoptosis in CRC cells and inhibit their proliferation, and the mechanism underlying these effects involves increasing the level of MST1 in CRC cells, which then upregulates the expression of pro-apoptotic proteins, such as BAX, but downregulates the expression of anti-apoptotic proteins, such as BCL-2. Recent studies have found that the expression levels of MST1 and YAP1 in human colon cancer tissue are significantly higher than those in the adjacent tissues [23,24]. In human primary colon cancer, adenomatous colonic polyposis, or mouse multiple intestinal tumor, the expression of YAP is upregulated, which could also promote the growth of transplanted tumors in a mouse model.…”

Section: Discussionmentioning

confidence: 99%

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine

Liu

Xia

Zhang

et al. 2018

Libyan Journal of Medicine

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The aim of this study was to observe the impact of the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway on apoptosis in colorectal cancer (CRC) cells induced by Taurine (Tau). Caco-2 and SW620 cells transfected with p-enhanced green fluorescent protein (EGFP)-MST1 or short interfering RNA (siRNA)-MST1 were treated with Tau for 48 h. Apoptosis was detected by flow cytometry, and the levels of MST1 and JNK were detected by western blotting. Compared with the control group, 80 mM Tau could significantly induce apoptosis of CRC cells, and the apoptotic rate increased with increasing Tau concentration (P < 0.01). Meanwhile, the protein levels of MST1 and phosphorylated (p)-JNK in Caco-2 cells increased significantly (P < 0.01). The apoptotic rate of the p-EGFP-MST1 plasmid-transfected cancer cells was significantly higher than that of the control group (P < 0.05); however, the apoptotic rate of the p-EGFP-MST1+Tau group was increased further (P < 0.01). Silencing the MST1 gene could decrease the apoptotic rate of cancer cells, and Tau treatment could reverse this decrease. Blocking the JNK signaling pathway significantly reduced the Tau-induced apoptotic rate of CRC cells. Thus, the MST1-JNK pathway plays an important role in Tau-induced apoptosis of CRC cells.

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“…Moreover, expression of TAZ showed an exceptionally strong association with poor patient survival from non-small lung cancer and thyroid carcinoma (25,26). Alterations in this gene and/or its molecular partners YAP and TEAD have also been reported in cancers derived from colon, lung, liver, or esophagus (27)(28)(29). A very recent study by Camargo and his group has shown that the tumor suppressor LKB1, which is known for its ability to regulate cellular metabolism through AMPK activation, also regulates Hippo signaling (30).…”

Section: Introductionmentioning

confidence: 99%

Identification, Mechanism of Action, and Antitumor Activity of a Small Molecule Inhibitor of Hippo, TGF-β, and Wnt Signaling Pathways

Basu

Lettan

Damodaran

et al. 2014

Molecular Cancer Therapeutics

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Embryonic signaling pathways, in particular those mediated by Wnt and TGF-b, are known to play key roles in tumor progression through the induction of epithelial-mesenchymal transition (EMT). Their simultaneous targeting could therefore represent a desirable anticancer strategy. On the basis of recent findings that both Wnt and TGF-b-associated pathways are regulated by Hippo signaling in mammalian cells, we reasoned that targeting the latter would be more effective in inhibiting EMT. In a search for such inhibitors, we identified a small molecule (C19) with remarkable inhibitory activity not only against Hippo, but also against Wnt and TGF-b pathways. C19 inhibited cancer cell migration, proliferation, and resistance to doxorubicin in vitro, and exerted strong antitumor activity in a mouse tumor model. Mechanistically, C19 induced GSK3-b-mediated degradation of the Hippo transducer TAZ, through activation of the Hippo kinases Mst/Lats and the tumor suppressor kinase AMPK upstream of the degradation complex. Overall, this study identified C19 as a multi-EMT pathway inhibitor with a unique mechanism of action. The findings that both AMPK and Mst/Lats mediate the antitumor activity of C19 shed light on a potential cross-talk between metabolic and organ size control pathways in regulating cancer progression. By simultaneously targeting these two pathways, C19 may represent a new type of agents to suppress cancer progression and/or its recurrence.

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Wnt/β-Catenin Signaling Regulates Yes-associated Protein (YAP) Gene Expression in Colorectal Carcinoma Cells

Cited by 245 publications

References 43 publications

MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1

MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine

Identification, Mechanism of Action, and Antitumor Activity of a Small Molecule Inhibitor of Hippo, TGF-β, and Wnt Signaling Pathways

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