c-Met up-regulates the expression of PD-L1 through MAPK/NF-κBp65 pathway

Xu, Rui; Liu, Xinkuang; Li, Amin; Wang, Jintao; Liang, Jiaojiao; Gao, Jiafeng; Tang, Xi-can

doi:10.1007/s00109-022-02179-2

Cited by 18 publications

(10 citation statements)

References 44 publications

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“…The tumors in most patients with advanced HCC that are treated with the first-line drug, sorafenib, develop drug resistance [14,15]. Sorafenib-acquired resistance reportedly involves a variety of mechanisms, including multiple-signal pathway crosstalk; abnormal expression of tyrosine kinase receptors, such as PDGFR-β, c-kit, Flt-3, VEGFR and EGFR; epithelial-mesenchymal transition (EMT); and cancer stem-cell differentiation [16][17][18].…”

Section: Discussionmentioning

confidence: 99%

IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways

Cai

Wang

et al. 2023

BMC Cancer

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Background Insulin-like growth factor-1 receptor (IGF-1R) promotes cell proliferation and migration and inhibitsapoptosis, all of which can contribute to the development of cancers. Method This study investigated the effect and mechanism of IGF-1R in mediating the desensitization of hepatocellular carcinoma (HCC) to sorafenib. Results IGF-1R, highly expressed in the HCC cell lines SK-Hep1 and HepG2, promotes cell proliferation, migration, and anti-apoptosis through PI3K / Akt and RAS / Raf / ERK signaling pathways, resulting in HCC resistance to sorafenib. Knockdown of IGF-1R by RNA interference decreased proliferation and cell migration and upregulation of sorafenib-induced apoptosis of HCC cells. In vivo studies demonstrated that IGF-1R knockdown inhibited the growth of SK-Hep1 xenografts. Conclusion These data are evidence that IGF-1R participates in regulating the survival and cell growth of HCC through the PI3K / Akt and RAS / Raf / ERK signaling pathways. Intervention in the expression of IGF-1R may increase the inhibitory effect of sorafenib on HCC.

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Section: Discussionmentioning

confidence: 99%

IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways

Cai

Wang

et al. 2023

BMC Cancer

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“…As an important immunosuppressive molecule, PD‐L1 is abnormally expressed in tumor cells and is the main factor encouraging tumor immune escape ability 12 . Additionally, the expression of PD‐L1 was related to the MAPK pathway 44 . Hence, we overexpressed KIT and simultaneously activated the MAPK pathway using its activator anisomycin.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of immune escape mediated by receptor tyrosine kinase KIT in thyroid cancer

Luo

et al. 2023

Immunity Inflam & Disease

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Objective Thyroid cancer (TC) is one of the fastest‐growing malignant tumors. This study sought to explore the mechanism of immune escape mediated by receptor tyrosine kinase (KIT) in TC. Methods The expression microarray of TC was acquired through the GEO database, and the difference analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were carried out. KIT levels in TC cell lines (K1/SW579/BCPAP) and human normal thyroid cells were detected using reverse transcription quantitative polymerase chain reaction and western blot analysis. TC cells were transfected with overexpressed (oe)‐KIT and CD8+ T cells were cocultured with SW579 cells. Subsequently, cell proliferation, migration, and invasion abilities, CD8+ T cell proliferation, cytokine levels (interferon‐γ [IFN‐γ]/tumor necrosis factor‐α [TNF‐α]) were determined using colony formation assay, Transwell assays, flow cytometry, and enzyme‐linked immunosorbent assay. The phosphorylation of MAPK pathway‐related protein (ERK) was measured by western blot analysis. After transfection with oe‐KIT, cells were treated with anisomycin (an activator of the MAPK pathway), and the protein levels of p‐ERK/ERK and programmed death‐ligand 1 (PD‐L1) were detected. Results Differentially expressed genes (N = 2472) were obtained from the GEO database. KIT was reduced in TC samples and lower in tumor cells than those in normal cells. Overexpression of KIT inhibited immune escape of TC cells. Specifically, the proliferation, migration, and invasion abilities of TC cells were lowered, the proliferation level of CD8+ T cells was elevated, and IFN‐γ and TNF‐α levels were increased. KIT inhibited the activation of the MAPK pathway in TC cells and downregulated PD‐L1. Conclusion KIT suppressed immune escape of TC by blocking the activation of the MAPK pathway and downregulating PD‐L1.

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“…In addition, c-Met and PD-L1 were shown to be co-overexpressed in sorafenib-resistant cell lines, and c-Met promoted the expression of PD-L1 through the MAPK/NF-κBp65 cascade. The overexpressed PD-L1 in turn facilitates sorafenib resistance ( Xu et al, 2022 ). By activating Sterol regulatory element-binding protein 1 (SREBP-1) via the PI3K/AKT signaling, PD-L1 promoted EMT in sorafenib-resistant HCC cell lines ( Xu et al, 2020 ).…”

Section: Relationships Between Sorafenib Resistance and Tumor Microen...mentioning

confidence: 99%

Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights

et al. 2022

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Sorafenib, a multi-kinase inhibitor with antiangiogenic, antiproliferative, and proapoptotic properties, is the first-line treatment for patients with late-stage hepatocellular carcinoma (HCC). However, the therapeutic effect remains limited due to sorafenib resistance. Only about 30% of HCC patients respond well to the treatment, and the resistance almost inevitably happens within 6 months. Thus, it is critical to elucidate the underlying mechanisms and identify effective approaches to improve the therapeutic outcome. According to recent studies, tumor microenvironment (TME) and immune escape play critical roles in tumor occurrence, metastasis and anti-cancer drug resistance. The relevant mechanisms were focusing on hypoxia, tumor-associated immune-suppressive cells, and immunosuppressive molecules. In this review, we focus on sorafenib resistance and its relationship with liver cancer immune microenvironment, highlighting the importance of breaking sorafenib resistance in HCC.

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c-Met up-regulates the expression of PD-L1 through MAPK/NF-κBp65 pathway

Cited by 18 publications

References 44 publications

IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways

IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways

Mechanism of immune escape mediated by receptor tyrosine kinase KIT in thyroid cancer

Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights

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