STMN-1 Gene: A Predictor of Survival in Stage IIA Esophageal Squamous Cell Carcinoma After Ivor-Lewis Esophagectomy?

Akhtar, Javed; Wang, Zhou; Yu, Chunhua; Zhang, Zhi Ping; Bi, Ming

doi:10.1245/s10434-013-3215-z

Cited by 24 publications

(32 citation statements)

References 29 publications

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“…We have previously reported that STMN1 is frequently overexpressed in esophageal squamous cell carcinoma tissue and significantly upregulated in esophageal cancer cell lines [12]. Our clinical data suggested that STMN1 is a predictor of survival in esophageal cancer, and laboratory data confirmed that upregulated STMN1 level in cell lines was oncogenic.…”

Section: Discussionsupporting

confidence: 66%

“…STMN1 was originally identified as a phosphoprotein upregulated in leukemia [11]. Since then, it has also been reported to be overexpressed in solid tumors, including in our previous research, and we found that STMN1 was highly overexpressed in esophageal squamous cell carcinoma and was related with malignancy of the disease and poor clinical outcome [12]. In our recent research, we also reported that STMN1 is associated with lymphatic metastatic recurrence in pN0 ESCC [13].…”

Section: Introductionsupporting

confidence: 51%

“…The sequences of STMN-1 shRNA are as follows: 5′-TTATTAGCTTCCAT TTTGT-3′; 5′-TCTCTTCTATTGCCTTCTG-3′ and 5′-TTAT TAACCATTCAAGTCC-3′. Production of lentiviral shRNA, packaging, tranfection, and transduction were performed based on our previous study [12]. For cell infection, viral supernatants were supplemented with 6 μg/mL polybrene and incubated with cells for 24 h. Esophageal cancer cell lines were transduced by the lentiviral particles followed by puromycin selection (1 μg/mL) for 10 days.…”

Section: Transfection Lentivirus Production and Transductionmentioning

confidence: 99%

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Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma

2015

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Stathmin (STMN1) regulates microtubule dynamics by promoting depolymerization of microtubules and/or preventing polymerization of tubulin heterodimers. Several studies have shown that overexpression of STMN1 has been linked to chemoresistance of paclitaxel and vinblastine in tumor cells. This study aimed to investigate the effects of STMN1 silencing on chemosensitivities of paclitaxel or vinblastine in esophageal squamous cell carcinoma (ESCC). Immunocytochemistry and immunofluorescence assays showed that STMN1 gene was highly expressed in Eca109 and TE-1 cells. We demonstrated that lentiviral-mediated STMN1 short hairpin RNA (shRNA) specifically and efficiently downregulated STMN1 expression in Eca109 and TE-1 cells. The sensitivity of STMN1-silencing shRNA-transfected Eca109 and TE-1 cells increased 191.4- and 179.3-fold to paclitaxel, and 21.3- and 28.4-fold to vincristine, respectively. Flow cytometry and mitotic index assays showed that knockdown of STMN1 in Eca109 and TE-1 cells led to cell cycle arrest in G2/M phase. After treatment with paclitaxel or vincristine, STMN1-silencing shRNA-transfected Eca109 and TE-1 cells were more likely to enter G2 but less likely to enter mitosis than control cells. Therefore, these data suggests that silencing STMN1 gene could increase sensitivity of ESCC to paclitaxel and vincristine through G2/M phase block.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionsupporting

confidence: 51%

Section: Transfection Lentivirus Production and Transductionmentioning

confidence: 99%

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Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma

2015

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“…Overexpression of STMN1 in human cancer not only disrupts normal cell-cycle progression but, more importantly, facilitates polyploidy/aneuploidy of the targeted cells [15]. Stathmin 1 has been implicated in both G1-S and G2-M checkpoint control of cell-cycle progression by influencing the dynamics of microtubule formation and progression of the cell cycle [30]. Kang et al [42] found that aberrant p53 immunoreactivity was associated with higher STMN1 expression in gastric adenocarcinoma, suggesting that overexpression of STMN1 might be partially due to inactivation of tumor-suppressor gene p53.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis

Mao

Chen

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Several recent studies have demonstrated that Stathmin 1expression may be closely associated with prognosis in patients with various types of cancers. In the present study, we conducted a meta-analysis of all available studies in the English literature to assess the prognostic value of Stathmin 1expression in patients with solid cancers. Methods: The online databases PubMed, Embase, and Web of Science were searched for literature regarding Stathmin 1 and its association with patient outcomes associated with solid cancers. Results: A total of 23 articles including 26 studies that contained 5 335 patients were retrieved and analyzed. Our results indicated that high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio [HR] = 2.17, 95% confidence interval [CI]: 1.81–2.60), disease-free survival (DFS) (HR = 2.46, 95% CI: 2.00–3.02), disease-specific survival (DSS) (HR = 1.98, 95% CI: 1.58– 2.47) and progression-free survival (PFS)/recurrence-free survival (RFS) (HR = 2.09, 95% CI: 1.51–2.89). Furthermore, the association of high Stathmin 1 expression with poor survival was significant even for sub-group analyses of different tumor types, ethnicities, methods used to calculate HRs, detected methods, and analysis types. Conclusion: In summary, this meta-analysis determined that high Stathmin 1 expression is associated with poor prognosis in patients with solid cancers and expression of this protein could be a clinically useful prognostic biomarker.

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“…STMN1 promotes microtubule depolymerisation by sequestering tubulin (Marklund et al , 1996; Rubin and Atweh, 2004; Budhachandra et al , 2008) and stimulating catastrophes (Howell et al , 1999). High STMN1 expression is associated with poor prognosis in a variety of human cancers such as nasopharyngeal carcinoma (Cheng et al , 2008; Hsu et al , 2014), distal oesophageal adenocarcinoma (Akhtar et al , 2014a), oesophageal squamous cell carcinoma (Akhtar et al , 2014b), breast cancer (Golouh et al , 2008), hepatocellular carcinoma (Hsieh et al , 2010), cholangiocarcinoma (Watanabe et al , 2014), prostate cancer (Mistry and Atweh, 2006), colorectal cancer (Wu et al , 2014), and non-small cell lung cancer (NSCLC; Nie et al , 2015). STMN1 was suggested as a possible prognostic marker and a potential therapeutic target for GC (Jeon et al , 2010; Kang et al , 2012; Ke et al , 2013).…”

mentioning

confidence: 99%

High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients

et al. 2017

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Background:Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases.Methods:Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines.Results:Multivariate and Kaplan–Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis.Conclusions:STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.

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STMN-1 Gene: A Predictor of Survival in Stage IIA Esophageal Squamous Cell Carcinoma After Ivor-Lewis Esophagectomy?

Abstract: Even localized ESCC are potential to relapse with poor prognosis. This study demonstrates that STMN-1 level is an independent prognostic factor after Ivor-Lewis esophagectomy. In addition, assessment of STMN-1 level could improve stratification of stage IIA ESCC patients.

Cited by 24 publications

References 29 publications

Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma

Anti-STMN1 therapy improves sensitivity to antimicrotubule drugs in esophageal squamous cell carcinoma

Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis

High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients

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