Skp2 and Jab1 Expression Are Associated with Inverse Expression of p27&lt;sup&gt;KIP1&lt;/sup&gt; and Poor Prognosis in Oral Squamous Cell Carcinomas

Shintani, Satoru; Li, Chunnun; Mihara, Mariko; Hino, Shinjiro; Nakashiro, Koh‐ichi; Hamakawa, Hiroyuki

doi:10.1159/000074649

Cited by 72 publications

(73 citation statements)

References 21 publications

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“…Further statistical analysis revealed that amplification and overexpression of SKP2 were significantly associated with positive lymph node metastasis and tumor stage. Immunohistochemical analyses by other investigators also revealed that overexpression of SKP2 was associated with lymph node metastasis in oral squamous cell carcinoma (19) and laryngeal squamous cell carcinoma (20). Significantly inverse correlation between SKP2 and p27 expression was found in ESCC, which was concordance with reports in other tumors (16,17,21).…”

Section: Discussionsupporting

confidence: 72%

Suppression of Anoikis by SKP2 Amplification and Overexpression Promotes Metastasis of Esophageal Squamous Cell Carcinoma

Wang

Ye³

et al. 2009

Molecular Cancer Research

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The gene of SKP2, located on chromosome 5p13, plays a critical role in cell cycle progression, especially at the G 1 -S transition, putatively through its control of several cell cycle regulator proteins including p27 kip1 , p21 cip1 , p57 kip2 , p130, cyclin E, and c-Myc. Previous studies in this laboratory revealed that gain of chromosome 5p was often seen in esophageal squamous cell carcinoma (ESCC). In the present study, we examined the amplification status and expression level of SKP2 in ESCC and investigated its clinicopathologic significance. Amplification and elevated expression of SKP2 correlated significantly with tumor stage and positive lymph node metastasis (P < 0.05). The SKP2 protein expression level as determined by immunohistochemical staining showed a significant inverse correlation with p27 protein. In vivo assay showed that inhibition of SKP2 expression also decreased tumor growth and lung metastasis of ESCC cells. At the molecular level, knockdown of SKP2 by RNA interference inhibited cell migration and invasion ability. Knockdown of SKP2 expression sensitized cancer cells to anoikis, and a wobble mutant of SKP2 that is resistant to SKP2 small interfering RNA can rescue this effect. Expression level of pAkt decreased after SKP2 knockdown. Treatment of cells with phosphoinositidyl 3-kinase inhibitor (LY294002) and constitutively activator (insulin-like growth factor I) had significant effects on the anoikis of SKP2 RNA interference cells. These results show for the first time that SKP2 is amplified and overexpressed in ESCC. Elevated expression of SKP2 protected cancer cells from anoikis, and this effect was mediated, at least in part, by the phosphoinositidyl 3-kinase-Akt pathway.

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Section: Discussionsupporting

confidence: 72%

Suppression of Anoikis by SKP2 Amplification and Overexpression Promotes Metastasis of Esophageal Squamous Cell Carcinoma

Wang

Ye³

et al. 2009

Molecular Cancer Research

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“…13,30 To our knowledge, only one previous study has been published on the expression of p27 kip1 and Jab1 proteins in systemic anaplastic large cell lymphoma (ALCL), and that report also showed Jab1 and p27 kip1 expression were inversely correlated. 15 In the current study, 71.55% NHLs showed Jab1 positive expression and was significantly associated with the clinical stage. Therefore, these results suggested that Jab1 protein, as a negative regulator of p27 kip1 , might contribute to the progression of NHLs.…”

Section: Discussionsupporting

confidence: 48%

“…Jun activation domain-binding protein 1 negatively regulate p27 kip1 in non-Hodgkin's lymphomas squamous cell carcinomas, 15 etc. George et al 16 found that p27 kip1 was absent or expressed at low levels in most systemic anaplastic large cell lymphoma (ALCL) and inversely correlated with Jab1.…”

Section: Research Papermentioning

confidence: 99%

Jun activation domain-binding protein 1 negatively regulate p27kip1 in non-Hodgkin’s lymphomas

Wang

Fei²,

Cheng³

et al. 2008

Cancer Biology & Therapy

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Objective: Recent evidences suggest that Jun activation domainbinding protein 1 (Jab1) specifically interacts with the Cdk inhibitor p27kip1 and induces nuclear export and subsequent degradation of p27kip1. The purpose of this study is to investigate whether Jab1 expression is correlated with p27kip1 level in NonHodgkin's Lymphomas (NHLs) and how it influenced the stability of p27kip1, as well as whether Jab1 expression is associated with clinicopathologic variables and prognosis of NHLs.Results: Immunohistochemical analysis showed that Jab1 expression was negatively associated with p27kip1 level and significantly associated with unfavorable clinicopathologic variables. Overexpression Jab1 in lymphoma cell lines Jurkat resulted in decreased p27kip1 level and advanced progression from G 1 to S phase of the cell cycle. Subcellular fractionation confirmed Jab1 could lead to nuclear export of p27kip1. Phosphorylation of p27kip1 at Ser10 and Thr157 was significantly increased after Jab1 transient transfected, while Thr187 phosphorylation was decreased. Immunoprecipitation demonstrated that Jab1 overexpression facilitated p27kip1 to dissociate from Cdk2 and associated with Cdk4. Finally, Survival analysis revealed that Jab1 overexpression is significantly associated with overall survival (p = 0.000). When Jab1 and p27kip1 are combined, patients with Jab1 + /p27kip1 -revealed poorer overall survival (p = 0.001). Multivariate analysis revealed that Jab1 protein is an independent prognostic indicator for overall survival.Methods: Immunohistochemical and/or Western blot analysis was done in 116 cases of NHLs and Jurkat cells.Conclusions: These findings suggest that Jab1 protein may contribute to the tumor progression through Jab1-mediated p27kip1 degradation and that control of Jab1 expression is a novel therapeutic target in patients with NHLs.

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“…Many studies have reported that JAB1 is overexpressed in different types of cancers. The overexpression of JAB1 is inversely associated with p27 levels and correlates with poor prognosis (Kouvaraki et al, 2003;Shintani et al, 2003;Osoegawa et al, 2006).…”

mentioning

confidence: 99%

C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer

Shi

Chen

et al. 2011

Oncogene

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In an earlier study we showed that C10ORF97 (chromosome-10, open reading frame-97) was expressed in almost all of the tissues and cell lines tested, and that it inhibited the growth of seven tumor cell lines, including two lung carcinoma cell lines (A549 and PG). Here, we show that C10ORF97 is downregulated in non-small-cell lung cancer (NSCLC) tissue compared with normal lung tissue. Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage-independent growth in soft agar) and motility (migration and adhesion). This tumor-suppressive function of C10ORF97 was also verified in vivo. We further found that C10ORF97 caused G 1 arrest of A549 cells and modulated the expression level of several cell-cycle regulators (such as CDK2, cyclin-E and p27). These effects of C10ORF97 were mediated by physical association between C10ORF97 and Jun-activating domain-binding protein-1 (JAB1), and blocking of JAB1-mediated translocation of p27 from the nucleus to the cytoplasm. Together, these results indicated that C10ORF97 functions as a novel tumor suppressor by modulating several key G 1 /S-regulatory proteins by interacting with JAB1. These findings led us to hypothesize that a single-nucleotide polymorphism (SNP) in the C10ORF97 gene that affects its expression might be associated with susceptibility to NSCLC. SNP216 C4T (rs2297882) in the C10ORF97 Kozak sequence was identified, and allele T of SNP216 suppressed C10ORF97 expression in vitro and in vivo. Furthermore, the TT genotype of SNP216 was associated with an increased risk of NSCLC (adjusted odds ratio ¼ 1.73 (95% confidence interval: 1.33-2.25), P ¼ 4.6 Â 10 -5). These data indicated that C10ORF97 is a tumor suppressor of NSCLC progression and C10ORF97-SNP216 may serve as a predictor of NSCLC.

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Skp2 and Jab1 Expression Are Associated with Inverse Expression of p27<sup>KIP1</sup> and Poor Prognosis in Oral Squamous Cell Carcinomas

Cited by 72 publications

References 21 publications

Suppression of Anoikis by SKP2 Amplification and Overexpression Promotes Metastasis of Esophageal Squamous Cell Carcinoma

Suppression of Anoikis by SKP2 Amplification and Overexpression Promotes Metastasis of Esophageal Squamous Cell Carcinoma

Jun activation domain-binding protein 1 negatively regulate p27kip1 in non-Hodgkin’s lymphomas

C10ORF97 is a novel tumor-suppressor gene of non-small-cell lung cancer and a functional variant of this gene increases the risk of non-small-cell lung cancer

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