Histone deacetylase inhibitor chidamide regulates the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL

Zhao, Linlin; Lv, Chengfang; Sun, Lili; Li, Qi; Wang, YuHuang; Wu, Min; Wang, Yuying; Guo, Zhibo; Bian, Sicheng; Kong, Desheng; Li, Lin; Wang, Yu; Zhou, Jin; Li, Yinghua

doi:10.1007/s10637-021-01079-5

Cited by 7 publications

(5 citation statements)

References 36 publications

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“…Moreover, our reviewed studies suggest that many of these inhibitors can inhibit the development of different cancers by blocking this signaling. However, the information on the suppression of this signaling mediated by these inhibitors is mainly from in vitro cell models [ 71 – 96 ]. Data from animal experiments, as well as clinical trials, are needed to confirm whether the anticancer effect of these inhibitors is related to Wnt/β-catenin signaling.…”

Section: Discussionmentioning

confidence: 99%

“…MGCD0103, also known as mocetinostat [ 95 ], is an inhibitor of Class I and IV HDACs and underwent a Phase II trial for treating cancers; it has the role of suppressing Wnt/β-catenin signaling as well. Additionally, chidamide [ 10 , 96 ], an inhibitor of class I and IV HDACs, is approved in China to treat cancer and can target Wnt/β-catenin signaling in cancer (Table 2 ). However, the molecular mechanisms related to this signaling inhibition mediated by these inhibitors in most cancers are not well clarified.…”

Section: Introductionmentioning

confidence: 99%

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The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

You

Kong

et al. 2022

Cell Mol Biol Lett

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Canonical Wnt/β-catenin signaling is a complex cell-communication mechanism that has a central role in the progression of various cancers. The cellular factors that participate in the regulation of this signaling are still not fully elucidated. Lysine acetylation is a significant protein modification which facilitates reversible regulation of the target protein function dependent on the activity of lysine acetyltransferases (KATs) and the catalytic function of lysine deacetylases (KDACs). Protein lysine acetylation has been classified into histone acetylation and non-histone protein acetylation. Histone acetylation is a kind of epigenetic modification, and it can modulate the transcription of important biological molecules in Wnt/β-catenin signaling. Additionally, as a type of post-translational modification, non-histone acetylation directly alters the function of the core molecules in Wnt/β-catenin signaling. Conversely, this signaling can regulate the expression and function of target molecules based on histone or non-histone protein acetylation. To date, various inhibitors targeting KATs and KDACs have been discovered, and some of these inhibitors exert their anti-tumor activity via blocking Wnt/β-catenin signaling. Here, we discuss the available evidence in understanding the complicated interaction of protein lysine acetylation with Wnt/β-catenin signaling, and lysine acetylation as a new target for cancer therapy via controlling this signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

You

Kong

et al. 2022

Cell Mol Biol Lett

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“…AKT/mTOR, MAPK, ATM-Chk2-p53-p21 (NKTCL) [317]. MYCN/DKK3-Wnt/β-catenin (B-ALL) [318]. Hedgehog signaling-miRNA-338-5p (glioma cells) [319].…”

Section: Multiple Myelomamentioning

confidence: 99%

Converting “cold” to “hot”: epigenetics strategies to improve immune therapy effect by regulating tumor‐associated immune suppressive cells

Tang,

Cui,

Liu

et al. 2024

Cancer Communications

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Significant developments in cancer treatment have been made since the advent of immune therapies. However, there are still some patients with malignant tumors who do not benefit from immunotherapy. Tumors without immunogenicity are called “cold” tumors which are unresponsive to immunotherapy, and the opposite are “hot” tumors. Immune suppressive cells (ISCs) refer to cells which can inhibit the immune response such as tumor‐associated macrophages (TAMs), myeloid‐derived suppressor cells (MDSCs), regulatory T (Treg) cells and so on. The more ISCs infiltrated, the weaker the immunogenicity of the tumor, showing the characteristics of “cold” tumor. The dysfunction of ISCs in the tumor microenvironment (TME) may play essential roles in insensitive therapeutic reaction. Previous studies have found that epigenetic mechanisms play an important role in the regulation of ISCs. Regulating ISCs may be a new approach to transforming “cold” tumors into “hot” tumors. Here, we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating ISCs. In addition, we summarized the mechanisms by which the epigenetic drugs convert immunotherapy‐insensitive tumors into immunotherapy‐sensitive tumors which would be an innovative tendency for future immunotherapy in “cold” tumor.

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“…MYCN is a member of the MYC proto‐oncogene family, which downregulates the expression of DKK3 54 . Chidamide was reported to inhibit the proliferation of B‐ALL leukemic cells by regulating the Wnt/β‐catenin pathway via a decrease in the expression of MYCN protein and an increase in the expression of DKK3 protein 55 …”

Section: Chidamide In Acute Lymphoblastic Leukemiamentioning

confidence: 99%

Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

Cao

Xue

et al. 2022

Hematological Oncology

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Epigenetic alterations frequently participate in the onset of hematological malignancies. Histone deacetylases (HDACs) are essential for regulating gene transcription and various signaling pathways. Targeting HDACs has become a novel treatment option for hematological malignancies. Chidamide is the first oral selective HDAC inhibitor for HDAC1, HDAC2, HDAC3, and HDAC10 and was first approved for the treatment of R/R peripheral T‐cell lymphoma by the China Food and Drug Administration in 2014. Chidamide was also approved under the name Hiyasta (HBI‐8000) in Japan in 2021. In vitro studies revealed that chidamide could inhibit proliferation and induce apoptosis via cell cycle arrest and the regulation of apoptotic proteins. In clinical studies, chidamide was also efficacious in multiple myeloma, acute leukemia and myelodysplastic syndrome. This review includes reported experimental and clinical data on chidamide monotherapy or chidamide treatment in combination with chemotherapy for various hematological malignancies, offering a rationale for the renewed exploration of this drug.

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Histone deacetylase inhibitor chidamide regulates the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL

Cited by 7 publications

References 36 publications

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

Converting “cold” to “hot”: epigenetics strategies to improve immune therapy effect by regulating tumor‐associated immune suppressive cells

Chidamide: Targeting epigenetic regulation in the treatment of hematological malignancy

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