Expression analysis and implication of Rab1A in gastrointestinal relevant tumor

Abstract

Gastrointestinal cancers have become increasingly prevalent worldwide. Previous studies have reported an oncogenic function of Rab1A in colorectal cancer and hepatocellular carcinomas via the mTOR pathway. However, the exact role of Rab1A in gastrointestinal cancers remains elusive. We detected significantly higher expression of Rab1A in the gastrointestinal tumor tissues compared to that in other cancer types following an in silico analysis of TGCA and GTEX databases. Furthermore, Rab1A was overexpressed in the gastrointestinal tumor tissues compared to the para-tumor tissues. Although Rab1A expression levels were not associated with the tumor-lymph node-metastasis (TNM) stage, Rab1A overexpression in the tumor tissues of a gastric cancer (GC) cohort was strongly correlated with poor prognosis in the patients. In addition, Rab1A knockdown significantly inhibited the in vitro proliferation and migration abilities of GC cells, as well as the growth of GC xenografts in vivo. Furthermore, a positive correlation was observed between Rab1A expression levels and that of different upstream/downstream mTOR targets. Taken together, Rab1A regulates the PI3K-AKT-mTORC1 pathway through the mTORC1 complex consisting of mTORC1, Rheb and Rab1A, and is a promising therapeutic target in GC.

Loss of DAB2IP Contributes to Cell Proliferation and Cisplatin Resistance in Gastric Cancer

“…The final staining score was determined by color intensity and positive cell rate, ranging 0–12 which was described in our previous study. 23 , 24 Patients were classified into two groups: scores 0–4 were considered as none or low, while 5–12 were considered as high expression.…”

“…A total of 20 µg protein was then separated by 8% SDS‑PAGE and then transferred onto a PVDF membranes according to methods described previously. 23 , 24 Antibodies against DAB2IP (dilution 1:1000; #ab87811, abcam), cyclin D1 (dilution 1:1000; 26939-1-AP, proteintech), p21 (dilution 1:1000; 10355-1-AP, proteintech), p-AKT (Ser473) (dilution 1:1000; #4058, CST), AKT (dilution 1:1000; #9272, CST), p-ERK (dilution 1:1000; #4370, CST), ERK (dilution 1:1000; #4695, CST) and Tubulin (dilution 1:2000; #AF5012, Beyotime) were used in this study.…”

Mycobacterium tuberculosis PE_PGRS20 and PE_PGRS47 Proteins Inhibit Autophagy by Interaction with Rab1A

“…Rab1A overexpression promotes mTORC1 signaling and oncogenic growth in an amino acid- and mTORC1-dependent manner. Conversely, Rab1A knockdown selectively attenuates the oncogenic growth of Rab1-overexpressing cancer cells ( 55 , 58 ). Thus, we hypothesize that the interaction of PE_PGRS proteins with Rab1A activates Rab1A GTP activity, resulting in mTOR activation and autophagy inhibition.…”

Clinical value and potential association of Rab1A and FoxM1 aberrant expression in colorectal cancer

“…Our results indicated that Rab1A expression was obviously linked to the depth of tumor invasion, lymph node invasion, venous invasion, and TNM staging. Rab1A overexpression is positively correlated with poor prognosis in several gastrointestinal cancers, such as CRC 6 and GC 13 . Consistent with these reports, our findings indicated that lower Rab1A expression indicated better prognosis in patients with CRC.…”

“…Previous studies indicated Rab1A acted as an oncogene and Rab1A overexpression promoted a worse prognosis in multiple cancer types such as gastric cancer 10 and hepatocellular carcinoma 11 . In addition, Rab1A overexpression has been positively associated with proliferation, migration, and drug-resistance in various cancers 12,13 .…”