Abstract 177P
Background
Membrane-associated 17 kDa protein (MAP17) is a non-glycosylated protein found in the plasma membrane and Golgi apparatus. This protein is overexpressed in human carcinoma cells and was suggested to play a key role in cancer progression. Here, we aimed to identify the role of MAP17 role in carcinoma progression using gastric cancer cell lines in vitro and human blood samples in vivo.
Methods
For this purpose, we performed cell culture experiments and Reverse transcription polymerase chain reaction, western blot, complementary DNA microarray, zymography, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), MAP17 knockdown with short hairpin RNA (shRNA), and a standard two-chamber invasion analyses. We also performed MAP17 enzyme-linked immunosorbent assays (ELISA) on 35 blood samples from patients who underwent surgery for gastric cancer.
Results
Our results confirmed the upregulation of MAP17 expression via hepatocyte growth factor (HGF) in gastric cancer cells. We also found that matrix metalloproteinase 9 (MMP9) expression is mediated by HGF. To identify the underlying mechanism, we treated cells with a phosphoinositol-3 kinase inhibitor (LY294002) and found that MMP9 levels were decreased by LY294002 treatment. The role of MAP17 in mediating MMP9 expression was also investigated via knockdown of MAP17. MAP17 knockdown led to decreased MMP9 expression and increased Rac1 expression. MAP17 knockdown also decreased HGF-mediated cell proliferation and invasion, and increased reactive oxygen species accumulation. A statistically significant reduction in MAP17 serum levels was also detected following total or subtotal gastrectomy with D2 lymphadenectomy in vivo.
Conclusions
Our findings highlight the role of MAP17 in cell proliferation, invasion, and metastasis in gastric cancer.
Clinical trial identification
IRB number (IRB): 2022-05-018-005.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.