RasGRP3, a Ras guanyl releasing protein 3 that contributes to malignant proliferation and aggressiveness in human esophageal squamous cell carcinoma

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide; however, clinical and pathological parameters have limited ability in discriminating between clinically significant and indolent ESCC. Since RasGRP3 transcript levels have prognostic value in discriminating ESCC with different clinical aggressiveness, we decided to investigate its putative oncogenic role in ESCC. We found that RasGRP3 was highly expressed in ESCC cells. Suppression of endogenous RasGRP3 expression in esophageal cell lines reduced Ras-GTP formation as well as AKT phosphorylation. RasGRP3 suppression also inhibited cell invasion and migration and reduced proliferation, demonstrating the importance of RasGRP3 for the transformed phenotype of melanoma cells. Suppression of RasGRP3 expression in these cells inhibited downstream RasGRP3 responses and suppressed cell growth and migration, confirming the functional role of RasGRP3 in the altered behaviour of these cells. This suggests that RasGRP3 may function as a Ras activator in the phosphoinositide signalling pathway and may potentially serve as a new therapeutic target.

Immunosignature Screening for Multiple Cancer Subtypes Based on Expression Rule

“…Recent publications have reported that such peptide is aligned to a group of specific proteins named phosphoinositide 3-kinase regulatory subunit 5 isoform 1/2 and sortilin-related receptor preproprotein (Altschul et al, 1990; Mount, 2007; Pruitt et al, 2014). Not all such identified proteins are lowly expressed in esophageal cancer, except for protein phosphoinositide 3-kinase regulatory subunit 5 (Zhang et al, 2018), validating the efficacy, and accuracy of our prediction. On the basis of the detailed expression level of such protein in serum provided by the Proteomics Database (Wilhelm et al, 2014; Schmidt et al, 2018) and the Cancer Proteomic Database (Arntzen et al, 2015), such protein has relatively high expression patterns in multiple tissue subtypes.…”

A Novel Ras--Related Signature Improves Prognostic Capacity in Oesophageal Squamous Cell Carcinoma

“…Accumulating evidence suggests that the Ras mutation rate can regulate the process of tumour development and progression, and is also involved in regulating the immune response to these tumours. ( Masliah-Planchon et al, 2016 ; Ryan and Corcoran, 2018 ; Zhang et al, 2018 ; Chen et al, 2019 ; Prior et al, 2020 ). However, systematic analysis of RAS in ESCC is still rare, and the underlying mechanism remains unclear.…”