C-Jun drives melanoma progression in PTEN wild type melanoma cells

Kappelmann‐Fenzl, Melanie; Gebhard, Claudia; Matthies, Alexander; Kuphal, Silke; Rehli, Michael; Boßerhoff, Anja

doi:10.1038/s41419-019-1821-9

Cited by 28 publications

(27 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Numerous studies have illuminated that the activation of CA9, STAT3, and FGF promotes the self-renewal capacity of CSCs [ 34 – 37 ]. Meanwhile, c-JUN, HMOX1, and CTGF play an oncogenic role in cancer [ 38 – 40 ]. Nevertheless, EGR1 , a member of a zinc finger transcription factor family, has been described as tumor suppressor in cancer progression [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Alpha-enolase (ENO1), identified as an antigen to monoclonal antibody 12C7, promotes the self-renewal and malignant phenotype of lung cancer stem cells by AMPK/mTOR pathway

et al. 2021

View full text Add to dashboard Cite

Background Tumor-associated antigens (TAAs) can be targeted in cancer therapy. We previously identified a monoclonal antibody (mAb) 12C7, which presented anti-tumor activity in lung cancer stem cells (LCSCs). Here, we aimed to identify the target antigen for 12C7 and confirm its role in LCSCs. Methods Immunofluorescence was used for antigen localization. After targeted antigen purification by electrophoresis and immunoblot, the antigen was identified by LC-MALDI-TOF/TOF mass spectrometry, immunofluorescence, and immunoprecipitation. The overexpression or silence of ENO1 was induced by lentiviral transduction. Self-renewal, growth, and invasion of LCSCs were evaluated by sphere formation, colony formation, and invasion assay, respectively. High-throughput transcriptome sequencing (RNA-seq) and bioinformatics analysis were performed to analyze downstream targets and pathways of targeted antigen. Results Targeted antigen showed a surface antigen expression pattern, and the 43–55 kDa protein band was identified as α-enolase (ENO1). Self-renewal, growth, and invasion abilities of LCSCs were remarkably inhibited by ENO1 downregulation, while enhanced by ENO1 upregulation. RNA-seq and bioinformatics analysis eventually screened 4 self-renewal-related and 6 invasion-related differentially expressed genes. GSEA analysis and qRT-PCR verified that ENO1 regulated self-renewal, invasion-related genes, and pathways. KEGG pathway analysis and immunoblot demonstrated that ENO1 inactivated AMPK pathway and activated mTOR pathway in LCSCs. Conclusions ENO1 is identified as a targeted antigen of mAb 12C7 and plays a pivotal role in facilitating self-renewal, growth, and invasion of LCSCs. These findings provide a potent therapeutic target for the stem cell therapy for lung cancer and have potential to improve the anti-tumor activity of 12C7.

show abstract

Section: Discussionmentioning

confidence: 99%

Alpha-enolase (ENO1), identified as an antigen to monoclonal antibody 12C7, promotes the self-renewal and malignant phenotype of lung cancer stem cells by AMPK/mTOR pathway

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The JNK/AP1 axis is commonly activated in benign and malignant melanoma, and promotes melanoma cell proliferation and invasion [148,[155][156][157][158]. One study showed that JNK is activated in over 75% benign nevi and it was predicted to have a role in restricting uncontrolled cell proliferation or survival.…”

Section: Jnk1 and Jnk2 In Melanoma Growth And Progressionmentioning

confidence: 99%

The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

Hammouda

Ford

Liu

et al. 2020

Cells

171

114

View full text Add to dashboard Cite

The c-Jun N-terminal kinases (JNKs), with its members JNK1, JNK2, and JNK3, is a subfamily of (MAPK) mitogen-activated protein kinases. JNK signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apoptosis, and inflammation. Dysregulation of JNK pathway is associated with a wide range of immune disorders and cancer. Our objective is to provide a review of JNK proteins and their upstream regulators and downstream effector molecules in common skin disorders, including psoriasis, dermal fibrosis, scleroderma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

show abstract

“…Phosphatase and tensin homolog (PTEN) was identified as a tumor suppressor and inhibited the development of multiple cancers [22][23][24]. Aside from cancers, recent studies also validated that PTEN was closely related with diabetes mellitus [25,26] and DR progression [27].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8

Fan

et al. 2020

Aging

View full text Add to dashboard Cite

Methyltransferase-like protein 3 (METTL3) regulates multiple cell functions and diseases by modulating N 6methyladenosine (m 6 A) modifications. However, it is still unclear whether METTL3 involves in the pathogenesis of diabetic retinopathy (DR). In the present study, we found that high-glucose inhibited RPE cell proliferation, promoted cell apoptosis and pyroptosis in a time-dependent manner. In addition, both METTL3 mRNA and miR-25-3p were low-expressed in the peripheral venous blood samples of diabetes mellitus (DM) patients compared to normal volunteers, and high-glucose inhibited METTL3 and miR-25-3p expressions in RPE cells. As expected, upregulation of METTL3 and miR-25-3p alleviated the cytotoxic effects of high-glucose on RPE cells, and knockdown of METTL3 and miR-25-3p had opposite effects. Additionally, METTL3 overexpression increased miR-25-3p levels in RPE cells in a microprocessor protein DGCR8-dependent manner, and miR-25-3p ablation abrogated the effects of overexpressed METTL3 on cell functions in high-glucose treated RPE cells. Furthermore, PTEN could be negatively regulated by miR-25-3p, and overexpression of METTL3 increased phosphorylated Akt (p-Akt) levels by targeting miR-25-3p/PTEN axis. Consistently, upregulation of PTEN abrogated the protective effects of METTL3 overexpression on RPE cells treated with high-glucose. Collectively, METTL3 rescued cell viability in highglucose treated RPE cells by targeting miR-25-3p/PTEN/Akt signaling cascade.

show abstract

C-Jun drives melanoma progression in PTEN wild type melanoma cells

Cited by 28 publications

References 50 publications

Alpha-enolase (ENO1), identified as an antigen to monoclonal antibody 12C7, promotes the self-renewal and malignant phenotype of lung cancer stem cells by AMPK/mTOR pathway

Alpha-enolase (ENO1), identified as an antigen to monoclonal antibody 12C7, promotes the self-renewal and malignant phenotype of lung cancer stem cells by AMPK/mTOR pathway

The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

Overexpression of METTL3 attenuates high-glucose induced RPE cell pyroptosis by regulating miR-25-3p/PTEN/Akt signaling cascade through DGCR8

Contact Info

Product

Resources

About