Abstract
BackgroundRapamycin-insensitive companion of mammalian target of rapamycin (Rictor) protein is a core subunit of mammalian target of rapamycin complex 2, and is associated with cancer progression. However, the biological function of Rictor in cancer, particularly its clinical relevance in gastric cancer (GC) remains largely unknown.MethodsRictor expression and its association with clinicopathologic characteristics in GC were analyzed by immunohistochemistry. Effect of Rictor and Caveolin-1 (Cav 1) on GC cells apoptosis was evaluated via overexpression experiment in vitro. Mechanisms of Rictor and Cav 1 in GC were explored through overexpression and knockdown, by immunofluorescence and western blot analyses.ResultsRictor was upregulated in GC, and mainly located in the cytoplasm of cancer cells. Moreover, higher Rictor levels were associated with worse prognosis. Rictor could inhibit GC cell apoptosis and promote cell growth in vitro. The results of immunofluorescence revealed that Cav 1 localized in GC cell membrane but did not co-localize with Rictor. Further, Rictor regulated apoptosis-related proteins, long non-coding RNAs and also activated cellular signaling, thereby positively regulating Cav 1 expression. This effect was attenuated by the Akt inhibitor ly294002. Cav 1 did not significantly affect the ability of Rictor to inhibit tumor cell apoptosis.ConclusionsRictor is upregulated in GC and associated with worse prognosis. It inhibits tumor apoptosis and activates Cav 1 through the Akt signaling pathway to inhibit the apoptosis of GC cells. Rictor is, therefore, a promising prognostic biomarker and possible therapeutic target in GC patients.
Highlights
Gastric cancer (GC) is one of the most common malignancies worldwide, ranking fifth in incidence and third in mortality [1]
We revealed an anti-apoptosis effect of Rapamycin-insensitive companion of mammalian target of rapamycin (Rictor) in GC cells and that Rictor activates Cav 1 through the Akt signaling pathway to inhibit the apoptosis of GC cells
We found that Rictor localized in the cytoplasm of cancer cells, but not in the surrounding stroma cells
Summary
Gastric cancer (GC) is one of the most common malignancies worldwide, ranking fifth in incidence and third in mortality [1]. East Asia is affected by GC, as indicated by the comparative high mortality [2]. Owing to high rates of metastasis and recurrence, the five-year overall survival rate for advanced GC is 20% [3]. With the continued advancements in molecular biology, signaling pathways and targeted therapy have gradually become the focus of GC research, and are expected to provide more effective means for the treatment of GC [4]. The biological function of Rictor in cancer, its clinical relevance in gastric cancer (GC) remains largely unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
