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

Bai, Tuya; Yokobori, Takehiko; Altan, Bolag; Ide, Munenori; Mochiki, Erito; Yanai, Mitsuhiro; Kimura, Akiharu; Kogure, Norimichi; Yanoma, Toru; Suzuki, Masaki; Bao, Pinjie; Kaira, Kyoichi; Asao, Takayuki; Katayama, Ayaka; Handa, Tadashi; Gombodorj, Navchaa; Nishiyama, Masahiko; Oyama, Tetsunari; Ogata, Kenichi; Kuwano, Hiroyuki

doi:10.1038/bjc.2017.76

Cited by 50 publications

(46 citation statements)

References 41 publications

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“…47,48 In chemoresistance-related reports, the high expression of STMN1 in gastric cancer is associated with chemoresistance, and the silencing of STMN1 expression in esophageal cancer increases its sensitivity to paclitaxel, which is consistent with our finding that STMN1 is highly expressed in drug-resistant cell lines. 49,50 There is a little report of TADLO1 associated with tumor or drug resistance. It is related to metabolism.…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma

degree

et al. 2018

Cancer Biology & Therapy

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Nasopharyngeal carcinoma (NPC) is a highly prevalent disease in Southeast Asia. The disease is typically diagnosed in the later stages, and chemotherapy resistance often causes treatment failure. To investigate the underlying mechanisms of drug resistance, we searched for chemoresistant-associated proteins in NPC and drug-resistant NPC cell lines using isobaric tags for relative and absolute quantitation combined with nano liquid chromatography-tandem mass spectrometry. The chemoresistant NPC cell lines CNE1DDP and CNE2DDP were resistant to 1 mg/L cisplatin, had resistant indexes of 4.58 and 2.63, respectively, and clearly grew more slowly than the NPC cell lines CNE1 and CNE2. Using three technical replicates, we identified 690 nonredundant proteins, 56 of which were differentially expressed in both groups of cell lines (CNE1 vs. CNE1DDP and CNE2 vs. CNE2DDP). Gene Ontology, KEGG pathway, and miRNA analyses and protein-protein interactions of differentially expressed proteins showed that proteins TRIM29, HSPB1, CLIC1, ANXA1, and STMN1, among others, may play a role in the mechanisms of chemoresistance in clinical therapy. The chemotherapy-resistant proteomic profiles obtained may allow the identification of novel biomarkers for early detection of chemoresistance in NPC and other cancers.

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Section: Discussionmentioning

confidence: 99%

iTRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma

degree

et al. 2018

Cancer Biology & Therapy

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“…has been suggested to be a marker of tumor resistance to taxanes (13)(14)(15)(16). LK-2 and RERF-LC-AI cells were treated with or without TXT and Ramucirumab in single and combination treatment settings, and then subjected to RNA-seq analysis.…”

Section: Stxbp4 As a Novel Therapeutic Targetmentioning

confidence: 99%

“…Needless to say, the TP53 gene is a key factor in tumorigenesis and tumor resistance to therapy in lung cancer (5)(6)(7)(8)(9), and ΔNp63 is a putative diagnostic marker for LSCC (12). STMN1 (oncoprotein 18 and LAP18) has been suggested to be a potent predictive marker for a variety of cancers including LSCC (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Syntaxin binding protein 4 as a novel therapeutic target and an effective biomarker for better treatment selection in lung squamous cell carcinoma: A theranostic study

Erkhem-Ochir

Kaira²,

Kawabata‐Iwakawa

et al. 2020

Preprint

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Abstract Background Lung squamous cell carcinoma (LSCC) remains a challenging disease to treat, and further improvements in prognosis are dependent upon the identification of LSCC-specific therapeutic biomarkers and/or targets. We previously found that Syntaxin Binding Protein 4 (STXBP4) plays a crucial role in lesion growth and, therefore, clinical outcomes in LSCC patients through regulation of tumor protein p63 (TP63) ubiquitination. Methods To clarify the potential of STXBP4 as a novel therapeutic target and/or a predictive biomarker of therapeutic response, we assessed its prognostic impact of the protein in 144 LSCC patients and examined whether its action pathway is distinct from those of currently used drugs in in vitro experiments including RNA-seq analysis through comparison with the other putative exploratory targets and/or markers. Results Kaplan–Meier analysis revealed that, along with ΔNp63 (an isoform of TP63) and vascular endothelial growth factor receptor 2 (VEGFR2), STXBP4 expression signified a worse prognosis in LSCC patients, both in terms of overall survival (OS, P = 0.002) and disease-free survival (DFS, P = 0.041). Multivariate analysis demonstrated STXBP4 to be an independent prognostic factor for poor DFS, while VEGFR2 (P < 0.001) and TP63 (ΔNp63, P < 0.05) were independent prognostic factors for poor OS. The action pathway of STXBP4 on suppression of TP63 (ΔNp63), which results in the and inhibits tumor growth, was unique: Ingenuity pathway analysis using the knowledge database and our RNA-seq analysis in human LSCC cell lines indicated that 35 pathways were activated or inactivated in association with STXBP4, but the action pathway of STXBP4 was distinct from those of other current drug targets: STXBP4, TP63 and KDR (VEGFR2 gene) formed a cluster independent from other target genes of tumor protein p53 (TP53), tubulin beta 3 (TUBB3), stathmin 1 (STMN1) and cluster of differentiation 274 (CD274: programmed cell death 1 ligand 1, PD-L1). STXBP4 itself appeared not to be a potent predictive marker of individual drug response, but we found that TP63, main action target of STXBP4, might be involved in drug resistance mechanisms of LSCC. Conclusion STXBP4 could afford a unique therapeutic target and a key to the development of precision medicine for LSCC patients.

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“…This association was described especially for microtubule-destabilizing drugs, as taxol, paclitaxel and docetaxel, but also for platinum, temozolamide, doxorubicin, arsenic acid, gefitinib and zoledronic acid. [110][111][112] More recently, upregulation of STMN1 expression by FOXM1 has been described in NSCLC. STMN1 overexpression was related to EMT and conferred multidrug tyrosine kinase inhibitors (TKIs) resistance on these cells.…”

Section: Stmn1 As Potential Therapeutic Targetmentioning

confidence: 99%

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

Serachi¹,

Marie²,

Oba-Shinjo³

2017

Medical Express

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OBJECTIVE:To analyze the associated expression of STMN1, MELK and FOXM1 in search of alternative drugable target in glioblastoma (GBM) and to review relevant functional roles of STMN1 in cancer biology. METHOD: STMN1, MELK and FOXM1 expressions were studied by quantitative PCR and their coexpressions were analyzed in two independent glioblastoma cohorts. A review of articles in indexed journals that addressed the multiple functional aspects of STMN1 was conducted, focusing on the most recent reports discussing its role in cancer, in chemoresistance and in upstream pathways involving MELK and FOXM1. RESULTS: Significant associated expressions of MELK and FOXM1 were observed with STMN1 in GBM. Additionally, the literature review highlighted the relevance of STMN1 in cancer progression. CONCLUSION: STMN1 is very important to induce events in cancer development and progression, as cellular proliferation, migration, and drug resistance. Therefore, STMN1 can be an important therapeutic target for a large number of human cancers. In glioblastoma, the most aggressive brain tumor, the MELK/FOXM1/STMN1 presented significant associated expressions, thus pointing MELK and FOXM1 as alternative targets for therapy instead of STMN1, which is highly expressed in normal brain tissue. Continuous functional research to understand the STMN1 signaling pathway is worthwhile to improve the therapeutic approaches in cancer.

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

Cited by 50 publications

References 41 publications

iTRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma

iTRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma

Syntaxin binding protein 4 as a novel therapeutic target and an effective biomarker for better treatment selection in lung squamous cell carcinoma: A theranostic study

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

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