Novel protein kinase inhibitor TT-00420 inhibits gallbladder cancer by inhibiting JNK/JUN-mediated signaling pathway

Miao, Huijie; Geng, Yajun; Li, Yang; Tang, Shibing; Feng, Feiling; Li, Weijian; Li, Yongsheng; Liu, Liguo; Zhang, Rui; Qiu, Shimei; Wu, Ying; Wang, Zeyu; Wang, Ziyi; Shao, Ziyu; Liu, Ke; Zou, Lu; Yang, Mao; Zhao, Yuhao; Chen, Chen; Li, Zhizhen; Zhang, Dadong; Peng, Peng; Qiang, Xiaoyan; Wu, Frank; He, Yongning; Chen, Luonan; Xiang, Dongxi; Jiang, Xiaoqing; Li, Maolan; Liu, Yun; Liu, Yingbin

doi:10.1007/s13402-022-00692-7

Cited by 6 publications

(2 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…JNK is considered as a potential target for cancer treatment. In GBC, JNK may promote the progression of tumor cells through the JNK/p38 MAPK [46] or JNK c-Jun pathway [47]. Here, we found that acylcarnitine contributes to the activation of JNK phosphorylation.…”

Section: Discussionmentioning

confidence: 60%

Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis

Yang,

Li,

Liu

et al. 2024

J Transl Med

Self Cite

View full text Add to dashboard Cite

Background The progression of gallbladder cancer (GBC) is accompanied by abnormal fatty acid β-oxidation (FAO) metabolism. Different types of lipids perform various biological functions. This study aimed to determine the role of acyl carnitines in the molecular mechanisms of GBC progression. Methods Distribution of lipids in GBC was described by LC–MS-based lipidomics. Cellular localization, expression level and full-length of lncBCL2L11 were detected using fluorescence in situ hybridization (FISH) assays, subcellular fractionation assay and 5′ and 3′ rapid amplification of the cDNA ends (RACE), respectively. In vitro and in vivo experiments were used to verify the biological function of lncBCL2L11 in GBC cells. Methylated RNA Immunoprecipitation (MeRIP) was performed to detect the methylation levels of lncBCL2L11. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were used to identify lncBCL2L11 interacting proteins. Co-Immunoprecipitation (Co-IP) and Western blot assay were performed to validate the regulatory mechanism of lncBCL2L11 and THO complex. Results Acylcarnitines were significantly up-regulated in GBC tissues. High serum triglycerides correlated to decreased survival in GBC patients and promoted tumor migration. LncBCL2L11 was identified in the joint analysis of highly metastatic cells and RNA sequencing data. LncBCl2L11 prevented the binding of THOC6 and THOC5 and causes the degradation of THOC5, thus promoting the accumulation of acylcarnitines in GBC cells, leading to the malignant progression of cancer cells. In addition, highly expressed acylcarnitines stabilized the expression of lncBCL2L11 through N6-methyladenosine methylation (m6A), forming a positive feedback regulation in tumor dissemination. Conclusions LncBCL2L11 is involved in gallbladder cancer metastasis through FAO metabolism. High lipid intake is associated with poor prognosis of GBC. Therefore, targeting lncBCL2L11 and its pathway-related proteins or reducing lipid intake may be significant for the treatment of GBC patients.

show abstract

Section: Discussionmentioning

confidence: 60%

Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis

Yang,

Li,

Liu

et al. 2024

J Transl Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…[ 2 ] The incidence of BTC is ranked as the fifth carcinoma in the gastrointestinal malignancies in China and is still rising. [ 3 , 4 ] Of note, the high and increasing mortality accounts for the poor prognosis with 5-year survival rate <5%. [ 5 ] Radical resection is currently the only possible curative treatment; however, >70% of BTC patients are diagnosed at the advanced stage and miss the opportunity for surgery, mainly due to the atypical symptoms and complex anatomical location at the early stage, which is not easily detectable.…”

Section: Introductionmentioning

confidence: 99%

Advances in immunotherapy for biliary tract cancers

Zhao,

Yang,

Feng

et al. 2023

Chinese Medical Journal

Self Cite

View full text Add to dashboard Cite

Biliary tract cancers (BTC) are a heterogeneous disease with poor prognosis, including gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC). Although surgery is currently the primary regimen to treat BTC, most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication. As a result, non-surgical therapy serves as the main intervention for advanced BTC. In recent years, immunotherapy has emerged as the one of the most promising therapies in a number of solid cancers, and it includes immune checkpoint inhibitors (ICIs) monotherapy or combined therapy, tumor vaccines, oncolytic virus immunotherapy, adoptive cell therapy (ACT), and cytokine therapy. However, these therapies have been practiced in limited clinical settings in patients with BTC. In this review, we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

show abstract

ELF3 promotes gemcitabine resistance through PKMYT1/CDK1 signaling pathway in gallbladder cancer

et al. 2023

View full text Add to dashboard Cite

Novel protein kinase inhibitor TT-00420 inhibits gallbladder cancer by inhibiting JNK/JUN-mediated signaling pathway

Cited by 6 publications

References 55 publications

Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis

Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis

Advances in immunotherapy for biliary tract cancers

ELF3 promotes gemcitabine resistance through PKMYT1/CDK1 signaling pathway in gallbladder cancer

Contact Info

Product

Resources

About