Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells

Ty, Jeon; Me, Han; Lee, YW; Ys, Lee; Gh, Kim; Ga, Song; Gy, Hur; Jy, Kim; Kim, Hyung Jun; Yoon, Sik; Sy, Baek; Bs, Kim; Jb, Kim; So, Oh

doi:10.1038/sj.bjc.6605537

Cited by 102 publications

(84 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…STMN was found extensively studied in relation to the cancer progression process (27,28) and in many studies directly linked to prostate cancer (29,30). STMN in our study was found downregulated multiple times (0.829, 0.829 and 0.783) as seen in Table I.…”

Section: Identification Of Differentially Expressed Proteins Upon Pdesupporting

confidence: 66%

PDEF downregulates stathmin expression in prostate cancer

et al. 2012

View full text Add to dashboard Cite

Abstract. The Ets proteins are a family of transcription factors characterized by an evolutionarily conserved DNA binding domain that controls key cellular processes. Prostate-derived Ets transcription factor (PDEF), a member of the Ets family, is reported to be present in tissues with high epithelial content, notably breast and prostate. However, the role of PDEF in cancer development is not fully understood. To gain insight into the molecular mechanisms associated with prostate cancer progression, we employed iTRAQ labeling followed by mass spectrometric (MS) analysis to identify candidate proteins that are differentially expressed in prostate cancer cells with or without PDEF. To this end, we overexpressed PDEF in PC3 human prostate cells using a tetracycline inducible system (Tet-On). Many differentially expressed proteins which play important roles in various cellular and biological processes were identified. Among them, stathmin (STMN), which is a microtubule (MT)-destabilizing protein, was found to be downregulated in multiple analyses. We demonstrated that re-expression of STMN reversed the antitumor properties of PDEF in PDEF-overexpressing PC3 cells. Using in vitro functional assays, we showed that STMN overexpression counteracted PDEF's effects against cell proliferation, colony formation and tumor migration. Similar results were further confirmed with the prostate cancer cell line CWR22rv1. In conclusion, many differentially expressed proteins were identified and STMN was found to be downregulated by PDEF.These results suggest that PDEF may inhibit prostate cancer progression by transcriptional downregulation of oncogenic STMN expression. Analyzing the association among differentially expressed proteins may provide a basis to better understand the molecular mechanisms underlying the process of cancer progression and development and further aid in designing therapeutics in the future. IntroductionProstate cancer is the most common cancer diagnosed among men and the second leading cause of death in American men, behind only lung cancer. The American Cancer Society (ACS) estimates about 1 man in 36 will die of prostate cancer (1). Although screening for prostate cancer, based on prostate specific antigen (PSA) has revolutionized early detection and diagnosis of the disease, the challenge that clinicians face are to determine which patients progress to aggressive disease (2,3). In order to determine the possibility of disease progression and ability to manage patient outcomes, it is necessary to better understand the molecular processes underlying the disease development and progression. Gene regulation is an important process in maintaining the integrity of cells for their proper growth and survival. Improper regulation of genes can lead to various diseases like cancer. The Ets family of transcription factors has been long investigated for their role in genetic loss of cellular homeostasis which results in development of various cancers. So far, 25 human and 26 murine Ets family members have been report...

show abstract

Section: Identification Of Differentially Expressed Proteins Upon Pdesupporting

confidence: 66%

PDEF downregulates stathmin expression in prostate cancer

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Stathmin1 is a microtubule-regulating protein that has an important role in the assembly and disassembly of the mitotic spindle. It has been shown to be involved in carcinogenesis, invasion, and metastasis of various cancers, including prostate, hepatocellular, and breast cancers (34,35,45,46). Since the cytotoxicity of ara-C is cell cyclespecific, stathmin1 could potentially affect the action of ara-C on the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

“…associated or cell cycle-regulating protein (34,35), it could be involved in mechanisms of resistance to the cell cycle-specific agent ara-C.…”

Section: Proteome Analysis Of Cem/ara-c Cellsmentioning

confidence: 99%

Characterization of cytarabine-resistant leukemic cell lines established from five different blood cell lineages using gene expression and proteomic analyses

Yamauchi

2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Cytarabine (ara-C) is the key drug for treatment of acute myeloid leukemia. Since intracellular cytarabine triphosphate (ara-CTP) is an active metabolite of ara-C, factors that reduce the amount of ara-CTP are known to induce drug resistance. However, these factors do not fully explain the development of resistance to ara-C. The present study was conducted to search for new candidate ara-C resistance factors, including those that are unrelated to ara-CTP production.

show abstract

“…2 In addition to its role in mitosis and cell cycle progression, STMN1 is involved in a wide variety of human cancers, including gastric cancer, nasopharyngeal carcinoma, colorectal cancer, and endometrial carcinoma, etc. [3][4][5][6] For example, Kang et al 7 showed that STMN1 was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas.…”

mentioning

confidence: 99%

Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer

Nie

Gan

et al. 2015

Laboratory Investigation

View full text Add to dashboard Cite

Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. However, the clinical significance of STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined. The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect STMN1 protein expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung cancer cell lines was evaluated by small interfering RNA-mediated depletion followed by analyses of cell proliferation and invasion. We found that the STMN1 mRNA and protein levels in NSCLC tissues were significantly higher than those in the corresponding non-tumor tissues (Po0.001). In addition, increased STMN1 expression was correlated with poor tumor differentiation (Po0.001), large tumor size (P ¼ 0.022), advanced N stage (P ¼ 0.033), and advanced TNM stage (Po0.001). Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression showed significantly worse survival. Moreover, multivariate analysis indicates that higher STMN1 protein expression was an independent prognostic factor of disease-specific survival (HR 2.247, 95%CI 1.320-3.825, P ¼ 0.003). Finally, the knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular proliferation and invasion. Our findings suggest that STMN1 may have an important role in NSCLC progression and could serve as a potential prognostic marker for patients with NSCLC.

show abstract

Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells

Cited by 102 publications

References 27 publications

PDEF downregulates stathmin expression in prostate cancer

PDEF downregulates stathmin expression in prostate cancer

Characterization of cytarabine-resistant leukemic cell lines established from five different blood cell lineages using gene expression and proteomic analyses

Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer

Contact Info

Product

Resources

About