Stathmin is overexpressed and regulated by mutant p53 in oral squamous cell carcinoma

Abstract

BackgroundThe aim of this study was to investigate the oncogenic function and regulatory mechanism of stathmin in oral squamous cell carcinoma (OSCC).MethodsTwo-dimensional electrophoresis and liquid chromatography-tandem mass chromatography were applied to screen differentiated proteins during carcinogenesis in OSCC. Cell Counting Kit-8 (CCK-8) assays, colony formation, migration, flow cytometry, immunofluorescence and a xenograft model were used to detect the function of stathmin. The correlation between stathmin and p53 expression was analyzed using immunohistochemistry. Mutant/wild type p53 plasmids and small interfering RNA were used to examine the regulation of stathmin. Chromatin immunoprecipitation assays and luciferase assays were performed to detect the transcriptional activation of stathmin by p53.ResultsOverexpression of stathmin was screened and confirmed in OSCC patients and cell lines. Silencing expression of stathmin inhibited proliferation, colony formation and migration and promoted apoptosis. Poly ADP ribose polymerase (PARP) and cyclin-dependent kinase 1 (cdc2) were activated after silencing the expression of stathmin. Suppression of tumorigenicity was also confirmed in vivo. Mutant p53 transcriptionally activated the expression of stathmin in HN6 and HN13 cancer cells, but not in HN30 cells harboring wild type p53.ConclusionsThese results suggest that stathmin acts as an oncogene and is transcriptionally regulated by mutant p53, but not by wild-type p53. Stathmin could be a potential anti-tumor therapeutic target in OSCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0575-4) contains supplementary material, which is available to authorized users.

A novel IFNα-induced long noncoding RNA negatively regulates immunosuppression by interrupting H3K27 acetylation in head and neck squamous cell carcinoma

“…Immunohistochemistry (IHC) and immunofluorescence were performed as described in our previous study [18], with primary antibodies against PD-L1, galectin-9, H3K27ac and GCN5 (Cell Signaling Technology, Danvers, MA, USA), and Ki-67 (Proteintech, Rocky Hill, NJ, USA). The staining intensity was assessed as follows: 0 = negative; 1 = weak; 2 = moderate; 3 = strong.…”

Stathmin guides personalized therapy in oral squamous cell carcinoma

“…The primary antibodies included stathmin (#ab52630, 1:500 dilution; Abcam), Ki‐67 (#19972‐1‐AP, 1:50 dilution; Proteintech) and Bub1 (budding uninhibited by benzimidazoles 1, #13330‐1‐AP, 1:100 dilution; Proteintech). Stathmin immunohistochemical staining score was evaluated as previously described …”

“…Stathmin, an important microtubule‐destabilizing protein, is shown to be overexpressed in many human malignancies, including hepatocellular carcinoma and lung, gastric, breast, and head and neck cancers . Our previous study suggested that stathmin acts as an oncogene and could be a potential antitumor therapeutic biomarker in OSCC . Several studies have shown that overexpression of stathmin influences the resistance of docetaxel and cisplatin .…”

Relevant coexpression of STMN1, MELK and FOXM1 in glioblastoma and review of the impact of STMN1 in cancer biology

“…101 Corroborating these observations, STMN1 inhibition in cancer cells harboring TP53 mutation has decreased cell proliferation and viability, increased apoptosis and suppressed tumorigenicity, suggesting that STMN1 is required for the survival of p53--mutant cells. [102][103][104][105] Recently, it was suggested that overexpressed STMN1 interacts with p53 and contributes to the gain-of-function of p53. 105 Altogether, these data suggest that targeting STMN1 may be an interesting approach to treat different types of cancers with aberrant p53 function.…”

“…[102][103][104][105] Recently, it was suggested that overexpressed STMN1 interacts with p53 and contributes to the gain-of-function of p53. 105 Altogether, these data suggest that targeting STMN1 may be an interesting approach to treat different types of cancers with aberrant p53 function.…”