2,4-Diamino-Quinazoline, a Wnt Signaling Inhibitor, Suppresses Gastric Cancer Progression and Metastasis

Chang, Te‐Sheng; Lu, Chung‐Kuang; Hsieh, Yung‐Yu; Wei, Kuo‐Liang; Chen, Wei-Ming; Tung, Sui-Yi; Wu, Cheng‐Shyong; Chan, Michael W.Y.; Chiang, Ming-Ko

doi:10.3390/ijms21165901

Cited by 9 publications

(4 citation statements)

References 46 publications

(48 reference statements)

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“…The data from databases and articles showed high expression of β-catenin in gastric cancer at transcription and translation levels [ 47 , 48 ]. This signaling is considered a therapeutic target for gastric cancer treatment [ 49 , 50 ]. Our study shows that the accumulation of nuclear β-catenin promoted proliferation, migration, and invasion of gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells

et al. 2021

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Ubiquitin-proteasome pathway has emerged as therapeutic targets for cancer. GEPIA database analysis showed that the expression of ubiquitin-associated protein 2 like (UBAP2L) in gastric cancer specimens was significantly higher than that in non-tumor tissue, and its high expression is associated with poor survival of gastric cancer patients. This study aims to investigate the role of UBAP2L in gastric cancer. Real-time PCR and western blot results showed that UBAP2L expression was upregulated in gastric cancer cell lines. Loss- and gain-of-function experiments demonstrated that silencing of UBAP2L inhibited proliferation, migration and invasion, and induced apoptosis of gastric cancer cells, and overexpression of UBAP2L played opposite roles. Nude mice inoculated with UBAP2L-silenced gastric cancer cells generated smaller xenografted tumors in vivo . Furthermore, UBAP2L activated Wnt/β-catenin signaling – the accumulation of nuclear β-catenin and the expression of its downstream targets (cyclin D1, AXIN-2 and c-MYC) was facilitated, whereas knockdown of UBAP2L deactivated this signaling. The tumor-suppressing effect of UBAP2L silencing was abolished by forced activation of β-catenin S33A . UBAP2L has been confirmed as a novel and direct target of miR-148b-3p. The anti-tumor effect of miR-148b-3p was partly reversed by UBAP2L overexpression. The expression of miR-148b-3p was negatively correlated with that of UBAP2L in gastric cancer samples. Overall, our study indicates that UBAP2L is required to maintain malignant behavior of gastric cancer cells, which involves the activation of Wnt/β-catenin signaling pathway. We propose UBAP2L as a potential therapeutic target against gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells

et al. 2021

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“…In 2020, Chang et al. found that 2,4-Diaminoquinazoline (2,4-DAQ), a selective inhibitor of LEF1, inhibits the expression of AXIN2, MYC and LGR5 and suppresses the proliferation, migration and invasion of gastric cancer cells ( 93 ). The oral Compound E7386 selectively inhibited the interaction of β-catenin with the β-catenin transcriptional coactivator CREB-binding protein (CBP) and exerted high antitumor activity in a human gastric cancer xenograft tumor model ( 94 ).…”

Section: Molecular Agents Targeting the Wnt Pathwaymentioning

confidence: 99%

Wnt signaling in gastric cancer: current progress and future prospects

Han,

Yang,

Zhu

et al. 2024

Front. Oncol.

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Levels of the Wnt pathway components are abnormally altered in gastric cancer cells, leading to malignant cell proliferation, invasion and metastasis, poor prognosis and chemoresistance. Therefore, it is important to understand the mechanism of Wnt signaling pathway in gastric cancer. We systematically reviewed the molecular mechanisms of the Wnt pathway in gastric cancer development; and summarize the progression and the challenges of research on molecular agents of the Wnt pathway.

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“…able to reduce the expression of the β-catenin target genes c-Myc, Axin2 and LGR5, and inhibit the proliferation and viability of CSCs. More importantly, 2,4-DAQ may reduce the migratory and invasive activities of tumor cells, suppress the growth of xenograft tumors and reduce the final tumor weights with few side effects and low drug toxicity (58). DHME, a chemically synthesized derivative of the fungal polyphenol hispolon has been indicated to block signaling of the Wnt canonical pathway by inhibiting the transcriptional activity of the β-catenin/TCF complex.…”

Section: Advances In Anti-colorectal Tumor Therapy Targeting the Cano...mentioning

confidence: 99%

Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review)

Chen

Deng

2022

Int J Oncol

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Colorectal cancer (CRC) is one of the most common malignant tumor types occurring in the digestive system. The incidence of CRC has exhibits yearly increases and the mortality rate among patients with CRC is high. The Wnt/β-catenin signaling pathway, which is associated with carcinogenesis, is abnormally activated in CRC. Most patients with CRC have adenomatous polyposis coli mutations, while half of the remaining patients have β-catenin gene mutations. Therefore, targeting the Wnt/β-catenin signaling pathway for the treatment of CRC is of clinical value. In recent years, with in-depth research on the Wnt/β-catenin signaling pathway, inhibitors have been developed that are able to suppress or hinder the development and progression of CRC. In the present review, the role of the Wnt/β-catenin signaling pathway in CRC is summarized, the research status on Wnt/β-catenin pathway inhibitors is outlined and potential targets for inhibition of this pathway are presented. Contents 1. Introduction 2. Current status of CRC treatments 3. Overview of the Wnt signaling pathway 4. Role of the Wnt/β-catenin signaling pathway in the development and progression of CRC 5.

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2,4-Diamino-Quinazoline, a Wnt Signaling Inhibitor, Suppresses Gastric Cancer Progression and Metastasis

Cited by 9 publications

References 46 publications

Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells

Ubiquitin-associated protein 2 like (UBAP2L) enhances growth and metastasis of gastric cancer cells

Wnt signaling in gastric cancer: current progress and future prospects

Blocking the Wnt/β‑catenin signaling pathway to treat colorectal cancer: Strategies to improve current therapies (Review)

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