MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in gastric cancer cells

Abstract

BackgroundImmunotherapy and its mechanisms are being studied in a wide variety of cancers. Programmed cell death ligand 1 (PDL1) is associated with immune evasion in numerous tumor types. Here, we aimed to assess the relationship between metastasis associated in colon cancer‐1 (MACC1) and PDL1 and examine their effects on gastric cancer (GC) tumor immunity.MethodsThe expression of MACC1, c‐Met, and PDL1 in human GC tissues was first assessed using quantitative RT‐PCR (qRT‐PCR) and immunohistochemistry. We then focused on the relationships among MACC1, c‐Met, and PDL1 using RT‐PCR and western blotting after cell transfection and inhibitor treatment in vitro and on the identification of their roles in immune killing in vitro and in vivo.ResultsWe found that expression of MACC1, c‐Met, and PDL1 was upregulated in human GC tissues, and there was a positive correlation between the expression levels. In addition, we found that ectopic expression of MACC1 (silencing and overexpression by transfection) resulted in corresponding changes in c‐Met and PDL1 expression levels, and c‐Met/AKT/mTOR pathway inhibitors (SU11274, MK2206, and rapamycin) blocked the regulation of PDL1 expression by MACC1. Furthermore, silencing of MACC1 led to an increase in antitumor and immune killing in vitro and in vivo, and overexpression of MACC1 resulted in a decrease in tumor immunity in vitro and in vivo.ConclusionsFrom these data, we infer that MACC1 regulates PDL1 expression and tumor immunity through the c‐Met/AKT/mTOR pathway in GC cells and suggest that MACC1 may be a therapeutic target for GC immunotherapy.

Helicobacter Pylori UreB Upregulates the Expression of PD-L1 through Myh9 /mTOR Pathway and Inhibits the Activation of CD8+ T Cells

“…And, there are about 100 genes associated with mTOR signal pathway. It is consistent with the report that c-Met/AKT/mTOR pathway activated by MACC1 (metastasis associated in colon cancer-1) contributes to the PD-L1 expression in gastric cancer cells and induces tumor growth in vivo (Tong et al, 2019). We found that H. pylori contributes to the activation of mTOR as well as the PD-L1 expression during H. pylori infection whereas PD-L1 were downregulated when UreB was depleted ( Figure S3C).…”

“…At least, we found a direct interaction between UreB and the heat shock protein family of host cells, so a further research focused on HSP mediated pathogenic mechanism during H. pylori infection will be valuable. mTOR was reported to regulate the expression of PD-L1 in gastric cancer (Tong et al, 2019), vice versa, PD-L1 promotes the proliferation of HNSCC cells through mTOR (Zheng et al, 2019). UreB upregulated immunosuppressive molecular PD-L1 through mTOR but not PI3K/AKT.…”

High CENPM mRNA expression and its prognostic significance in hepatocellular carcinoma: a study based on data mining

“…A recent study found that abnormal HGF/c-Met upregulation and activation are often observed in bladder cancer [30]. Studies have also found that metastasis associated with colon cancer 1 (MACC1) regulates PDL1 expression and tumor immunity in gastric cancer (GC) cells through the c-Met/AKT/mTOR pathway [31]. We hypothesized that CENPM may regulate the expression of c-Met, leading to the occurrence of HCC, and more related research is needed.…”

NSD1 stimulated survival and migration of gastric cancer cells through WNT10B

“…The early diagnosis and precise treatment for GC become an important medical and social problem [13]. GC is often occult-onset with no specific symptoms, and patients are often in the advanced stage at the time of diagnosis [14]. Moreover, GC has high metastasis, and traditional radiotherapy and chemotherapy have little effects [15].…”