AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-β1/Smad3 pathway

Deng, Liming; Bao, Wenming; Zhang, Baofu; Zhang, Sina; Chen, Ziyan; Zhu, Xuewen; He, Bangjie; Wu, Lijun; Chen, Xiaohu; Deng, Tuo; Chen, Bo; Yu, Zhengping; Wang, Yi; Chen, Gang

doi:10.1038/s41419-023-06092-5

Cited by 4 publications

(2 citation statements)

References 53 publications

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“…The expression of AZGP1 is epigenetically repressed in PDA by histone deacetylation, thereby enabling TGF-β-induced EMT, apparently through the non-canonical TGF-β activation of ERK [ 305 ]. AZGP1 is also lost in other cancers, enabling TGF-β1-induced EMT [ 306 , 307 ]. Lenvatinib, an FDA-approved anti-cancer small chemical inhibitor of multiple tyrosine kinases, induced AZGP1 expression in cholangiocarcinoma where it led to the suppression of TGF-β1-induced EMT [ 306 ].…”

Section: Mechanism Of Tgf-βs-induced Tumor Progressionmentioning

confidence: 99%

“…AZGP1 is also lost in other cancers, enabling TGF-β1-induced EMT [ 306 , 307 ]. Lenvatinib, an FDA-approved anti-cancer small chemical inhibitor of multiple tyrosine kinases, induced AZGP1 expression in cholangiocarcinoma where it led to the suppression of TGF-β1-induced EMT [ 306 ]. Consistent with its role in modulating TGF-β signaling, the overexpression of AZGP1 was shown to prevent fibrosis in a mouse model of kidney fibrosis [ 308 ].…”

Section: Mechanism Of Tgf-βs-induced Tumor Progressionmentioning

confidence: 99%

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Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective

Danielpour

2024

Pharmaceuticals

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The TGF-β family is a group of 25 kDa secretory cytokines, in mammals consisting of three dimeric isoforms (TGF-βs 1, 2, and 3), each encoded on a separate gene with unique regulatory elements. Each isoform plays unique, diverse, and pivotal roles in cell growth, survival, immune response, and differentiation. However, many researchers in the TGF-β field often mistakenly assume a uniform functionality among all three isoforms. Although TGF-βs are essential for normal development and many cellular and physiological processes, their dysregulated expression contributes significantly to various diseases. Notably, they drive conditions like fibrosis and tumor metastasis/progression. To counter these pathologies, extensive efforts have been directed towards targeting TGF-βs, resulting in the development of a range of TGF-β inhibitors. Despite some clinical success, these agents have yet to reach their full potential in the treatment of cancers. A significant challenge rests in effectively targeting TGF-βs’ pathological functions while preserving their physiological roles. Many existing approaches collectively target all three isoforms, failing to target just the specific deregulated ones. Additionally, most strategies tackle the entire TGF-β signaling pathway instead of focusing on disease-specific components or preferentially targeting tumors. This review gives a unique historical overview of the TGF-β field often missed in other reviews and provides a current landscape of TGF-β research, emphasizing isoform-specific functions and disease implications. The review then delves into ongoing therapeutic strategies in cancer, stressing the need for more tools that target specific isoforms and disease-related pathway components, advocating mechanism-based and refined approaches to enhance the effectiveness of TGF-β-targeted cancer therapies.

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Section: Mechanism Of Tgf-βs-induced Tumor Progressionmentioning

confidence: 99%

Section: Mechanism Of Tgf-βs-induced Tumor Progressionmentioning

confidence: 99%

Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective

Danielpour

2024

Pharmaceuticals

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Degradation of AZGP1 suppresses the progression of breast cancer cells via TRIM25

Qin,

Yuan,

Yuan

et al. 2023

Environmental Toxicology

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Alpha‐2‐glycoprotein 1, zinc‐binding (AZGP1) is a secreted protein, which has been shown to be a potential biomarker of cancer progression; however, its roles in breast cancer are still unclear. Currently, we analyzed the online datasets and found that AZGP1 was highly expressed in breast cancer tissues and its expression was negatively correlated with the survival of breast cancer patients. Functional experiments through AZGP1 knockdown revealed that AZGP1 could promote the proliferation, migration, and invasion ability of breast cancer cells. In vivo experiments obtained a consistent result. Mechanistically, it was found that AZGP1 interacted with tripartite motif‐containing protein 25 (TRIM25), which subsequently promoted AZGP1 degradation through facilitating the ubiquitination. Furthermore, overexpression of TRIM25 partially reversed the promoting effects of AZGP1 overexpression on breast cancer progression. Therefore, this study indicates that AZGP1 might be a potential therapeutic target for breast cancer treatment.

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LINC01094: A key long non-coding RNA in the regulation of cancer progression and therapeutic targets

Yi,

Zhu,

Zhu

et al. 2024

Heliyon

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AZGP1 activation by lenvatinib suppresses intrahepatic cholangiocarcinoma epithelial-mesenchymal transition through the TGF-β1/Smad3 pathway

Cited by 4 publications

References 53 publications

Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective

Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective

Degradation of AZGP1 suppresses the progression of breast cancer cells via TRIM25

LINC01094: A key long non-coding RNA in the regulation of cancer progression and therapeutic targets

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