Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas

Abstract

BackgroundLung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member.MethodsBy means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history.ResultsmRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters.ConclusionsThis explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.

SI113, a Specific Inhibitor of the Sgk1 Kinase Activity that Counteracts Cancer Cell Proliferation

“…Given that Sgk1 expression in NSCLC patient samples significantly correlates with cancer malignancy and is thus considered a worse prognostic indicator [13], the in vivo use of a small molecule able to inhibit selectively Sgk1 kinase activity can specifically hit cancer cells, contemporarily sparing normal cells, characterized by a modest expression of the kinase Sgk1. On the other hand, the sometimes ambiguous results described for the clinical use of Akt inhibitors in cancer therapy [37,38], recently attributed to the high expression of Sgk3 [26],can carve out a peculiar role for Sgk inhibitors in blocking the Ras/PI3K/PTEN/Akt(Sgk)/mTOR pathway in specific neoplastic phenotypes [1].…”

“…Indeed, the anti-apoptotic function of Sgk1 suggests its possible involvement in human carcinogenesis. Sgk1 increased expression has been found in human tumors, like prostate cancer [12] and non-small cell lung cancer of the squamous subtype, where Sgk1 mRNA level correlates with several clinical prognostic indicators [13]. Sgk1 knockout mice appear to be resistant to the chemical carcinogens used for the induction of colon cancer [14].…”

Inhibition of Colonic Tumor Growth by the Selective SGK Inhibitor EMD638683

“…SGK1 is highly expressed in several tumor cells [4], such as colon cancer [4], myeloma [5], medulloblastoma [6], prostate cancer [7], ovarian tumors [8] and non-small cell lung cancer [9]. On the other hand, down-regulation of SGK1 in some tumors has been reported, including adenomatous polyposis coli (APC) [3,4,10].…”

The SGK1 Kinase Inhibitor SI113 Sensitizes Theranostic Effects of the 64CuCl2 in Human Glioblastoma Multiforme Cells

“…SGK1 is regulated by insulin [22][23][24], IGF-1 [25], glucocorticoids [26] and IL-2 [27]. Increased SGK1 expression has been documented in several human tumors [19,[28][29][30]. It has been demonstrated that SGK1 regulates cell survival, proliferation and differentiation via phosphorylation of MDM2, which governs p53 stability and degradation [31].…”