Maternal embryonic leucine zipper kinase in tumor cells and tumor microenvironment: An emerging player and promising therapeutic opportunity

Tang, Bufu; Yan, Ruochen; Wang, Siwei; Zeng, Zhao‐Chong; Shi-Suo, Du

doi:10.1016/j.canlet.2023.216126

Cited by 5 publications

(5 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cross-DEGs were submit to the STRING database (https://www.string-db.org/) to create the protein-protein interactions (PPI) with a minimum required interaction score of 0.7. Then Cytoscape software (version 3.9.1) was utilized to visualize the regulatory network 26,31 and the plugin of CytoHubba in Cytoscape 32 was performed to identify hub genes in the PPI network based on Degree.…”

Section: Protein-protein Network Analysismentioning

confidence: 99%

“…[22][23][24][25] A diverse range of protein substrates have been identified to interact with MELK and regulate its activity through phosphorylation-dependent mechanisms. Activation of MELK is triggered by various stress stimuli, which subsequently promote the activation of apoptosis signal-regulated kinase 1 (ASK1), 26 transforming growth factor-β (TGF-β) 27 and p53 signaling pathways. 26 Activated MELK plays a role in regulating numerous cellular functions, including cell proliferation, cell cycle arrest, spliceosome assembly, stem cell self-renewal, metabolism, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…Activation of MELK is triggered by various stress stimuli, which subsequently promote the activation of apoptosis signal-regulated kinase 1 (ASK1), 26 transforming growth factor-β (TGF-β) 27 and p53 signaling pathways. 26 Activated MELK plays a role in regulating numerous cellular functions, including cell proliferation, cell cycle arrest, spliceosome assembly, stem cell self-renewal, metabolism, and apoptosis. 28,29 In lung cancer, it has been demonstrated that the overexpression of MELK stimulates the proliferation and metastasis of LUAD cells.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK

Ma,

Cui,

Zhu

et al. 2024

DDDT

View full text Add to dashboard Cite

Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1-(E) -1-(2-hydroxy-5-chlorophenyl) -3-(3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma. Methods: The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules. Results: HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments. Conclusion: Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.

show abstract

Section: Protein-protein Network Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK

Ma,

Cui,

Zhu

et al. 2024

DDDT

View full text Add to dashboard Cite

show abstract

“…M1-type macrophages typically release Th1 cytokines, exerting pro-inflammatory and anti-tumor effects ( 40 , 41 ). However, TAMs in the TME predominantly exhibit the M2 subtype and can induce angiogenesis and tumor invasion by secreting Th2 cytokines ( 42 , 43 ). NK cells can eliminate target cells through the release of granzymes and perforin or by facilitating antibody-dependent cytotoxicity via their Fc receptors ( 44 , 45 ).…”

Section: Overview Of the Tmementioning

confidence: 99%

Recent advances in understanding the immune microenvironment in ovarian cancer

Chen,

Yang,

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

The occurrence of ovarian cancer (OC) is a major factor in women’s mortality rates. Despite progress in medical treatments, like new drugs targeting homologous recombination deficiency, survival rates for OC patients are still not ideal. The tumor microenvironment (TME) includes cancer cells, fibroblasts linked to cancer (CAFs), immune-inflammatory cells, and the substances these cells secrete, along with non-cellular components in the extracellular matrix (ECM). First, the TME mainly plays a role in inhibiting tumor growth and protecting normal cell survival. As tumors progress, the TME gradually becomes a place to promote tumor cell progression. Immune cells in the TME have attracted much attention as targets for immunotherapy. Immune checkpoint inhibitor (ICI) therapy has the potential to regulate the TME, suppressing factors that facilitate tumor advancement, reactivating immune cells, managing tumor growth, and extending the survival of patients with advanced cancer. This review presents an outline of current studies on the distinct cellular elements within the OC TME, detailing their main functions and possible signaling pathways. Additionally, we examine immunotherapy rechallenge in OC, with a specific emphasis on the biological reasons behind resistance to ICIs.

show abstract

“…In addition, the ferroptosis inducer erastin is verified to affect Th17 cell differentiation and IL-17 signaling pathway, which has a therapeutic potential in HCC immunotherapy ( Tang et al, 2020 ). A recent study has unveiled that knockout of SLC7A11, a ferroptosis-related gene, in macrophage reduces the recruitment and infiltration of tumor-associated macrophages by activating ferroptosis, which elevates PD-L1 expression in macrophages and improves the antitumor efficacy of anti-PD-L1 therapy ( Tang B. F. et al, 2023 ). Also, several novel therapies based on inducing ferroptosis in HCC cells have been demonstrated to enhance antitumor immunity, along with increased activated CD8 + T cells and matured dendritic cells but decreased myeloid-derived suppressor cells in tumor tissues ( Xu Q. et al, 2021 ; Chen et al, 2022a ).…”

Section: Ferroptosis In Hccmentioning

confidence: 99%

Role of ferroptosis and its non-coding RNA regulation in hepatocellular carcinoma

2023

View full text Add to dashboard Cite

Ferroptosis is a newly discovered form of programmed cell death that involves the accumulation of iron-dependent lipid peroxides and plays a vital role in the tumorigenesis, development, and drug resistance of various tumors such as hepatocellular carcinoma (HCC). As a hotspot in molecular biology, non-coding RNAs (ncRNAs) participate in the initiation and progression of HCC, either act as oncogenes or tumor suppressors. Recent studies have shown that ncRNAs can regulate ferroptosis in HCC cells, which would affect the tumor progression and drug resistance. Therefore, clarifying the underlying role of ferroptosis and the regulatory role of ncRNA on ferroptosis in HCC could develop new treatment interventions for this disease. This review briefly summarizes the role of ferroptosis and ferroptosis-related ncRNAs in HCC tumorigenesis, progression, treatment, drug resistance and prognosis, for the development of potential therapeutic strategies and prognostic markers in HCC patients.

show abstract

Maternal embryonic leucine zipper kinase in tumor cells and tumor microenvironment: An emerging player and promising therapeutic opportunity

Cited by 5 publications

References 140 publications

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK

A Novel Tetramethylpyrazine Chalcone Hybrid- HCTMPPK, as a Potential Anti-Lung Cancer Agent by Downregulating MELK

Recent advances in understanding the immune microenvironment in ovarian cancer

Role of ferroptosis and its non-coding RNA regulation in hepatocellular carcinoma

Contact Info

Product

Resources

About