N-Glycosylation at Asn291 Stabilizes TIM-4 and Promotes the Metastasis of NSCLC

Chen, Siyuan; Wang, Yuzhen; Li, Wen; Liang, Yan; Wang, Yingchun; Wu, Zhuanchang; Xu, Lixiang; Liang, Xiaohong; Ma, Chao; Gao, Lifen

doi:10.3389/fonc.2022.730530

Cited by 5 publications

(5 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In cell experiments, TIM-4 downregulated the expression of E-cadherin, a marker of the EMT and upregulated the expression of N-cadherin, vimentin and Slug, which confirmed that TIM-4 promoted the migration, invasion and EMT of lung cancer cells in vitro (18). In non-small cell lung cancer (NScLc) cells membrane, TIM-4 was extensively N-glycosylated at Asn291 and after the removal of N-glycosylation, the stability of TIM-4 protein was decreased and TIM-4 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated ERAd (87). Thus, the expression of TIM-4 on the cell surface was decreased, which suppressed TIM-4 mediated metastasis in NScLc, which could provide a valuable biomarker for developing drugs targeting N-glycosylation at Asn291 on TIM-4 (87).…”

Section: Regulatory Role Of Tim-4 In the Occurrence And Development O...mentioning

confidence: 60%

Function and characteristics of TIM‑4 in immune regulation and disease (Review)

Wang

Chen

et al. 2022

Int J Mol Med

View full text Add to dashboard Cite

T-cell/transmembrane immunoglobulin and mucin domain containing 4 (TIM-4) is a phosphatidylserine receptor that is mainly expressed on antigen-presenting cells and is involved in the recognition and efferocytosis of apoptotic cells. TIM-4 has been found to be expressed in immune cells such as natural killer T, B and mast cells and to participate in multiple aspects of immune regulation, suggesting that TIM-4 may be involved in a variety of immune-related diseases. Recent studies have confirmed that TIM-4 is also abnormally expressed in a variety of malignant tumor cells and is closely associated with the occurrence and development of tumors and the tumor immune microenvironment. The present study aimed to describe the expression and functional characteristics of TIM-4 in detail and to comprehensively discuss its role in pathophysiological processes such as infection, allergy, metabolism, autoimmunity and tumor immunity. The current review provided a comprehensive understanding of the functions and characteristics of TIM-4, as well as novel ideas for the diagnosis and treatment of diseases. Contents 1. Introduction 2. Regulatory role of TIM-4 in efferocytosis 3. Functional characteristics of TIM-4 in different immune cells 4. Regulatory role of TIM-4 in the occurrence and development of diseases 5. conclusion

show abstract

Section: Regulatory Role Of Tim-4 In the Occurrence And Development O...mentioning

confidence: 60%

Function and characteristics of TIM‑4 in immune regulation and disease (Review)

Wang

Chen

et al. 2022

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…The majority of transmembrane proteins are altered by N-glycosylation, and it has long been understood how crucial this modification is for cancer cells to metastasize. The finding suggests that at Asn291, TIM-4 showed N-glycosylation modification contributing towards NSCLC metastasis in vitro and in vivo [30] . The study provides evidence about significantly different levels of protein abundance and glycosylation of proteins involved migration and resistance to drugs using combined proteomic and N-glycoproteomic techniques to thoroughly describe cisplatin resistance in NSCLC cells related membrane proteins.…”

Section: Post Translational Modificationmentioning

confidence: 84%

Unraveling the Post-Translational Modifications and therapeutical approach in NSCLC pathogenesis

Gulhane¹,

Singh²

2023

Translational Oncology

View full text Add to dashboard Cite

“…As discussed earlier, the mechanism of TIMD4 is still unclear. However, its low expression has been associated with better overall survival in NSCLC, indicating its potential as a prognostic/predictive biomarker ( 81 , 83 , 110 ). Since our results did not show its association with the response (as observed in previous studies), we hypothesize that synergistic expression of circulating immune modulatory molecules such as CD80, CEA, etc., with TIMD4 may be playing their role in influencing its association.…”

Section: Discussionmentioning

confidence: 99%

Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression

Raza,

Mohsen,

Kanbour

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related morbidity and mortality worldwide. Immune checkpoint inhibitors (ICIs) including anti-PD-1 and anti-PD-L1 antibodies, have significantly changed the treatment outcomes with better overall survival, but only 15-40% of the patients respond to ICIs therapy. The search for predictive biomarkers of responses is warranted for better clinical outcomes. We aim here to identify pre-treatment soluble immune molecules as surrogate biomarkers for tissue PD-L1 (TPD-L1) status and as predictors of response to anti-PD-1/PD-L1 therapy in NSCLC patients. Sera from 31 metastatic NSCLC patients, eligible for anti-PD-1/PD-L1 or combined chemoimmunotherapy, were collected prior to treatment. Analysis of soluble biomarkers with TPD-L1 status showed significant up/down regulation of the immune inhibitory checkpoint markers (sSiglec7, sSiglec9, sULBP4 and sPD-L2) in patients with higher TPD-L1 (TPD-L1 >50%) expression. Moreover, correlation analysis showed significant positive linear correlation of soluble PD-L1 (sPD-L1) with higher TPD-L1 expression. Interestingly, only responders in the TPD-L1 >50% group showed significant down regulation of the immune inhibitory markers (sPD-L2, sTIMD4, sNectin2 and CEA). When responders vs. non-responders were compared, significant down regulation of other immune inhibitory biomarkers (sCD80, sTIMD4 and CEA) was recorded only in responding patients. In this, the optimal cut-off values of CD80 <91.7 pg/ml and CEA <1614 pg/ml were found to be significantly associated with better progression free survival (PFS). Indeed, multivariate analysis identified the cutoff-value of CEA <1614 pg/ml as an independent predictor of response in our patients. We identified here novel immune inhibitory/stimulatory soluble mediators as potential surrogate/predictive biomarkers for TPD-L1 status, treatment response and PFS in NSCLC patients treated with anti-PD-1/PD-L1 therapy.

show abstract

N-Glycosylation at Asn291 Stabilizes TIM-4 and Promotes the Metastasis of NSCLC

Cited by 5 publications

References 46 publications

Function and characteristics of TIM‑4 in immune regulation and disease (Review)

Function and characteristics of TIM‑4 in immune regulation and disease (Review)

Unraveling the Post-Translational Modifications and therapeutical approach in NSCLC pathogenesis

Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression

Contact Info

Product

Resources

About