Hyperphosphorylation of ribosomal protein S6 predicts unfavorable clinical survival in non-small cell lung cancer.

摘要: Ribosomal protein S6 (rpS6), a component of the 40S ribosomal subunit, is involved in multiple cellular bioactivities. However, its clinicopathological significance non-small cell lung cancer (NSCLC) poorly understood. Expressions total rpS6 (t-rpS6) and phosphorylated (Ser235/236, p-rpS6) were detected immunohistochemically 316 NSCLC tissues 82 adjacent controls, followed by statistical evaluation relationship between proteins expressions patients’ survivals to identify their prognostic values. Cytological experiments with overexpressing or silencing lentivirus human bronchial epithelial (HBE) lines performed explore potential mechanisms which affects clinical development NSCLC. Additionally, specific RNA interference for Akt1, Akt2, Akt3, Akt inhibitor subsequent bioactivity tests employed as well investigate upstream regulation rpS6. Positive rates t-rpS6 p-rpS6 both significantly increased tissues, compared controls (82.91 vs 62.20 % t-rpS6; 52.22 21.95 % p-rpS6; P < 0.001). only hyperphosphorylation rpS6, expressed either elevated alone ratio (p-rpS6/t-rpS6) no less than 0.67, was greatly associated unfavorable survival patients, especially cases at stage I (all The independent adverse value hyperphosphorylated confirmed multivariate Cox regression analysis (hazard ratios p-rpS6/t-rpS6 0.67 2.403, 4.311 respectively, Overexpression knockdown along parallel alterations p-rpS6, led decreased cells proliferations dependent on redistributions cycles P < 0.05). Cells migration invasion also changed Furthermore, overexpression Akt2 phosphorylation inhibition, rather Akt1 resulted striking dephosphorylation mTOR, p70S6K P < 0.05), without any change expressions. Further showed markedly accompanied variation proliferation, cycle distribution Hyperphosphorylation probably regulated Akt2/mTOR/p70S6K signaling pathway, closely relevant progression it might be served promising therapeutic target treatment.