Antigen Peptide Transporter 1 (TAP1) Promotes Resistance to MEK Inhibitors in Pancreatic Cancers

Li, Boya; Feng, Yu; Hou, Qiaoyun; Fu, Yan; Luo, Yongzhang

doi:10.3390/ijms23137168

Cited by 5 publications

(2 citation statements)

References 43 publications

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“…In ACC and DLBC, the expression of SLC35C1 was positively correlated with TAP1. A previous study reported that TAP1 promoted chemoresistance by enhancing the transport of MEKi out of PDAC cells, leading to reduced intracellular MEKi concentration and attenuated inhibition of KRAS signaling pathways 30 . Therefore, SLC35C1 can be a potential target to provide a new strategy for the treatment of PDAC by interfering with TAP1.…”

Section: Discussionmentioning

confidence: 99%

Systematic pan-cancer analysis identifies SLC35C1 as an immunological and prognostic biomarker

Xie

Wang

Chen

et al. 2023

Sci Rep

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GDP-amylose transporter protein 1 (SLC35C1) plays an important role in many types of cancer. Therefore, it is clinically important to further investigate the expression profile of SLC35C1 in human tumors to provide new molecular clues for the pathogenesis of glioma. In this study, we performed a comprehensive pan-cancer analysis of SLC35C1 using a series of bioinformatics approaches and validated its differential tissue expression and biological function. The results showed that SLC35C1 was aberrantly expressed in different types of tumors and significantly correlated with overall survival (OS) and progression-free interval (PFI). More importantly, the expression level of SLC35C1 was closely correlated with Tumor Microenvironment (TME), immune infiltration and immune-related genes. In addition, we found that SLC35C1 expression was also closely related to Tumor Mutation Burden (TMB), Microsatellite Instability (MSI) and antitumor drug sensitivity in various cancer types. Functional bioinformatics analysis indicated that SLC35C1 may be involved in multiple signaling pathways and biological processes in glioma. Based on SLC35C1 expression, a risk factor model was found to predict OS of glioma. In addition, in vitro experiments showed that SLC35C1 knockdown significantly inhibited the proliferation, migration and invasive ability of glioma cells, while SLC35C1 overexpression promoted proliferation, migration, invasion and colony formation of glioma cells. Finally, quantitative real-time PCR confirmed that SLC35C1 was highly expressed in gliomas.

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Section: Discussionmentioning

confidence: 99%

Systematic pan-cancer analysis identifies SLC35C1 as an immunological and prognostic biomarker

Xie

Wang

Chen

et al. 2023

Sci Rep

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“…The high expression of TAP1 may be associated with the production of more tumor neoantigens, which in turn initiate tumor immunity ( 23 ). On the other hand, recently, researchers have illustrated that the silent TAP1 induced the presentation of a TAP-independent peptide in human tumor cells, and thereby enhanced the effectiveness of immune potentiating therapies ( 24 , 25 ), which is additionally considered associated with tumor drug resistance ( 26 – 28 ). Therefore, it is necessary to uncover the role of TAP1 in ccRCC.…”

Section: Introductionmentioning

confidence: 99%

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation

et al. 2022

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Transporter associated with antigen processing 1(TAP1) serves as a protein to transport antigenic peptides from the surface of the endoplasmic reticulum to the lumen of the endoplasmic reticulum when the antigens are presented by major histocompatibility complex type I (MHC-I), which has been identified to play a critical role in antigen presentation in innate immunity. In tumors, the role of TAP1 seems to remain controversial. On the one hand, given the role of TAP1 in antigen presentation, it is indicated that high TAP1 expression corresponds to the emergence of more neoantigens epitopes that facilitate the recognition for phagocytes, T cells and other cells. On the other hand, the genetic ablation of transporter associated with antigen processing (TAP) results in the presentation of new class I-restricted epitopes encoded in house-keeping products. Opposite result has been revealed by studies in other tumors suggest, which implies a more complex function of TAP1. Therefore, it’s significant to clarify the role of TAP1 in clear cell renal cell carcinoma (ccRCC). In this study, we found the elevated expression levels in mRNA and protein of TAP1 in ccRCC tissues, which indicated a relatively worse prognosis. Transwell assay and Scratch assay in vitro demonstrated the promotive role of TAP1 in ccRCC migration as well as a significant role in metastasis. And the increased expression of TAP1 resulted in more immune cells infiltrated in cancer tissues. TAP1 was also demonstrated to be related to immune regulator genes, as gene set enrichment analysis (GSEA) indicated its significant role in immune regulation. The results of CancerSEA indicated the positive association of the high-level TAP1 expression with epithelial–mesenchymal transition (EMT) and the inverse association with Cell Cycle. The effective drugs were also predicted based on TAP1 expression, of which the high level was indeed associated with resistance to multiple drugs, but some effective drugs still identified based on high TAP1 expression. According to the analysis of various databases, the role of TAP1 in ccRCC was explored, especially in relationship of TAP1 with tumor microenvironment. These results indicate that TAP1 can serve as a potential target for treatment of ccRCC.

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Protein expression and localization of ABC transporters in pancreatic adenocarcinoma: Prognostic role of ABCC8

Cervenkova,

Palek,

Moulisova

et al. 2023

Pancreatology

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Antigen Peptide Transporter 1 (TAP1) Promotes Resistance to MEK Inhibitors in Pancreatic Cancers

Cited by 5 publications

References 43 publications

Systematic pan-cancer analysis identifies SLC35C1 as an immunological and prognostic biomarker

Systematic pan-cancer analysis identifies SLC35C1 as an immunological and prognostic biomarker

The expression and prognostic value of transporter 1, ATP binding cassette subfamily B member in clear cell renal cell cancer with experimental validation

Protein expression and localization of ABC transporters in pancreatic adenocarcinoma: Prognostic role of ABCC8

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