Abstract 3526: The mTORC2 component RICTOR plays a key role in lung cancer cell growth

RICTOR (Rapamycin-insensitive companion of mTOR protein) is a key component of mTORC2 (the mammalian target of rapamycin complex 2). One of the most-recognized targets for RICTOR-mTORC2 is AKT (Ser473). RICTOR also carries functions independent of mTORC2. RICTOR signaling has been suggested to play key roles in regulating cancer cell migration, invasion and metastasis in breast, ovarian, colorectal cancers and gliomas. The potential roles of RICTOR in lung cancer remain to be elucidated. We first examined the expression profile of RICTOR in primary lung tumor specimens and in lung cancer cell lines by immunohistochemistry. Among 125 FFPE patients' specimen, ninety nine were stained positive for RICTOR (intensity 1+ to 3+). More interestingly, the RICTOR IHC expression is stronger in squamous cell lung cancer in comparison to adenocarcinoma. Furthermore, twenty four out of 36 lung cancer cell lines showed positive RICTOR IHC staining. Thus, RICTOR is expressed in most lung tumors. To investigate the role of RICTOR in lung cancer cell growth, we found that RICTOR knockdown by siRNA reduced colony formation in A549, HCC827 and Calu3 cells, regardless of KRAS or EGFR mutational status (A549 is KRAS mutated whereas HCC827 is EGFR mutated). Western blot confirmed RICTOR knockdown and also decreased level of its downstream pAKT S473. We further blocked RICTOR signaling by utilizing inducible shRNAs of RICTOR. Similar inhibition of lung cancer cell growth was observed. Moreover, to t...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Molecular and Cellular Biology Source Type: research