A Comprehensive Pan-Cancer Analysis of the Potential Biological Functions and Prognosis Values of RICTOR

Abstract

The importance of the network defined by phosphatidylinositol-3-kinase (PI3K), AKT and mammalian target of rapamycin (mTOR) downstream of Receptor Tyrosine Kinase (RTK) has been recognized for many years. However, the central role of RICTOR (rapamycin-insensitive companion of mTOR) in this pathway has only recently come to light. The function of RICTOR in pan-cancer still needs to be systematically elucidated. In this study, we examined RICTOR’s molecular characteristics and clinical prognostic value by pan-cancer analysis. Our findings indicate that RICTOR was overexpressed in twelve cancer types, and a high RICTOR expression was linked to poor overall survival. Moreover, the CRISPR Achilles’ knockout analysis revealed that RICTOR was a critical gene for the survival of many tumor cells. Function analysis revealed that RICTOR-related genes were mainly involved in TOR signaling and cell growth. We further demonstrated that the RICTOR expression was significantly influenced by genetic alteration and DNA-methylation in multiple cancer types. Additionally, we found a positive relationship between RICTOR expression and the immune infiltration of macrophages and cancer-associated fibroblasts in Colon adenocarcinoma and Head and Neck squamous cell carcinoma. Finally, we validated the ability of RICTOR in sustaining tumor growth and invasion in the Hela cell line using cell-cycle analysis, the cell proliferation assay, and wound-healing assay. Our pan-cancer analysis highlights the critical role of RICTOR in tumor progression and its potential as a prognostic marker for various cancer types.

RICTOR/mTORC2 downregulation in BRAFV600E melanoma cells promotes resistance to BRAF/MEK inhibition

“…This discovery seems at odds with the well-established role of mTORC2 signaling in promoting cell growth and survival across various pathophysiological contexts [ 14 , 38 – 40 ], including melanoma progression [ 38 , 39 ]. However, our findings align with emerging evidence indicating tumor suppressive functions for mTORC2 in different settings [ 15 , 16 , 41 ].…”

Rictor—A Mediator of Progression and Metastasis in Lung Cancer

“…Several studies have demonstrated both RICTOR amplification and Rictor overexpression in different types of cancer, including lung cancer [9,17,[42][43][44][45][46][47]. Moreover, both RICTOR amplification and Rictor overexpression have been identified to be associated with poor prognosis and shorter survival [17,28,48]. In addition to amplification, a few other mechanisms (e.g., glucose-dependent acetylation or DNA methylation) have also been described to regulate Rictor expression and, therefore, mTORC2 activation [48,49].…”

“…Moreover, both RICTOR amplification and Rictor overexpression have been identified to be associated with poor prognosis and shorter survival [17,28,48]. In addition to amplification, a few other mechanisms (e.g., glucose-dependent acetylation or DNA methylation) have also been described to regulate Rictor expression and, therefore, mTORC2 activation [48,49]. However, further investigations are needed to reveal the exact role of these processes.…”