STNM1 in human cancers: role, function and potential therapy sensitizer

Liu, Ruiqi; Liang, Xiaodong; Guo, Haiwei; Li, Shuang; Yao, Wenming; Dong, Chenfang; Lu, Yutong; Tang, Jianming; Zhang, Haibo

doi:10.1016/j.cellsig.2023.110775

Cited by 4 publications

(3 citation statements)

References 188 publications

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“…CDC20 is a well-known regulator of the cell cycle, as it ensures the completion of cell division by controlling the correct segregation of chromosomes during the mitotic phase (M) [ 28 ]. STMN1 expression is increased in some malignancies, and inhibition of its expression may alter the division of tumor cells and thereby arrest cell growth in G2/M phase [ 29 ]. Our findings demonstrate that inhibiting the HSP90 protein with XL-888 results in a reduction in the expression of CDC20 and STMN1 genes, leading to cell cycle arrest in the G2/M phase in these cells.…”

Section: Resultsmentioning

confidence: 99%

Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Kaplan,

Gökşen Tosun

2024

Med Oncol

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Neuroblastoma is a common nervous system tumor in childhood, and current treatments are not adequate. HSP90 is a molecular chaperone protein that plays a critical role in the regulation of cancer-related proteins. HSP90 inhibition may exert anticancer effects by targeting cancer-related processes such as tumor growth, cell proliferation, metastasis, and apoptosis. Therefore, HSP90 inhibition is a promising strategy in the treatment of various types of cancer, and the development of next-generation inhibitors could potentially lead to more effective and safer treatments. XL-888 and Debio0932 is a next-generation HSP90 inhibitor and can inhibit the correct folding and stabilization of client proteins that cancer-associated HSP90 helps to fold correctly. In this study, we aimed to investigate the comprehensive molecular pathways of the anticancer activity of XL-888 and Debio0932 in human neuroblastoma cells SH-SY5Y. The cytotoxic effects of XL-888 and Debio0932 on the neuroblastoma cell line SH-SY5Y cells were evaluated by MTT assay. Then, the effect of these HSP90 inhibitors on the expression of important genes in cancer was revealed by Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) method. The qRT-PCR data were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) biological process tools. Finally, the effect of HSP90 inhibitors on HSP27, HSP70 and HSP90 protein expression was investigated by Western blotting analysis. The results revealed that XL-888 and Debio0932 had a role in regulating many cancer-related pathways such as migration, invasion, metastasis, angiogenesis, and apoptosis in SH-SY5Y cells. In conclusion, it shows that HSP90 inhibitors can be considered as a promising candidate in the treatment of neuroblastoma and resistance to chemotherapy.

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Section: Resultsmentioning

confidence: 99%

Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Kaplan,

Gökşen Tosun

2024

Med Oncol

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“…Moreover, ongoing studies target the identified genes ( ENO1, STMN1, PKM, CDK1 ), with therapies like enolase 1 depletion demonstrating efficacy across various tumor types by inhibiting glycolysis, growth, proliferation, migration, metastasis, and sensitizing tumors to chemotherapy and radiotherapy [ 63 ]. Targeting STMN1 and PKM2 also shows promise in reducing cell growth, metastasis, and increasing tumor cell apoptosis [ 93 , 94 ]. Despite these advancements, developing tumor-specific glycolysis inhibitors remains challenging amidst the critical role of the glycolysis pathway in immune cell function.…”

Section: Discussionmentioning

confidence: 99%

Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma

Dai,

Fan,

Xie

et al. 2024

Biomark Res

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Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy characterized by varied responses to treatment and prognoses. Understanding the metabolic characteristics driving DLBCL progression is crucial for developing personalized therapies. Methods This study utilized multiple omics technologies including single-cell transcriptomics (n = 5), bulk transcriptomics (n = 966), spatial transcriptomics (n = 10), immunohistochemistry (n = 34), multiple immunofluorescence (n = 20) and to elucidate the metabolic features of highly malignant DLBCL cells and tumor-associated macrophages (TAMs), along with their associated tumor microenvironment. Metabolic pathway analysis facilitated by scMetabolism, and integrated analysis via hdWGCNA, identified glycolysis genes correlating with malignancy, and the prognostic value of glycolysis genes (STMN1, ENO1, PKM, and CDK1) and TAMs were verified. Results High-glycolysis malignant DLBCL tissues exhibited an immunosuppressive microenvironment characterized by abundant IFN_TAMs (CD68+CXCL10+PD-L1+) and diminished CD8+ T cell infiltration. Glycolysis genes were positively correlated with malignancy degree. IFN_TAMs exhibited high glycolysis activity and closely communicating with high-malignancy DLBCL cells identified within datasets. The glycolysis score, evaluated by seven genes, emerged as an independent prognostic factor (HR = 1.796, 95% CI: 1.077–2.995, p = 0.025 and HR = 2.631, 95% CI: 1.207–5.735, p = 0.015) along with IFN_TAMs were positively correlated with poor survival (p < 0.05) in DLBCL. Immunohistochemical validation of glycolysis markers (STMN1, ENO1, PKM, and CDK1) and multiple immunofluorescence validation of IFN_TAMs underscored their prognostic value (p < 0.05) in DLBCL. Conclusions This study underscores the significance of glycolysis in tumor progression and modulation of the immune microenvironment. The identified glycolysis genes and IFN_TAMs represent potential prognostic markers and therapeutic targets in DLBCL.

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“…4h), are all reported to be related to immunotherapy. STNM1 has been reported as a poor prognostic marker in various cancers and can predict poor clinical outcomes of immunotherapy [85], and RSG1 has been reported as an oncogenic marker for poor immune microenvironment [86]. In addition, as an FDA-approved anti-parasitic drug, a recent study reported that ivermectin can induce immunogenic cancer cell death (ICD) and robust T cell infiltration, convert cold tumors into hot, and synergize with immune checkpoint blockade for the treatment of breast cancer [87].…”

Section: Combosc Uncovers the Potential Of Tumor Immune Microenvironm...mentioning

confidence: 99%

Personalized tumor combination therapy optimization using the single-cell transcriptome

Tang,

Fu,

Jin

et al. 2023

Genome Med

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Background The precise characterization of individual tumors and immune microenvironments using transcriptome sequencing has provided a great opportunity for successful personalized cancer treatment. However, the cancer treatment response is often characterized by in vitro assays or bulk transcriptomes that neglect the heterogeneity of malignant tumors in vivo and the immune microenvironment, motivating the need to use single-cell transcriptomes for personalized cancer treatment. Methods Here, we present comboSC, a computational proof-of-concept study to explore the feasibility of personalized cancer combination therapy optimization using single-cell transcriptomes. ComboSC provides a workable solution to stratify individual patient samples based on quantitative evaluation of their personalized immune microenvironment with single-cell RNA sequencing and maximize the translational potential of in vitro cellular response to unify the identification of synergistic drug/small molecule combinations or small molecules that can be paired with immune checkpoint inhibitors to boost immunotherapy from a large collection of small molecules and drugs, and finally prioritize them for personalized clinical use based on bipartition graph optimization. Results We apply comboSC to publicly available 119 single-cell transcriptome data from a comprehensive set of 119 tumor samples from 15 cancer types and validate the predicted drug combination with literature evidence, mining clinical trial data, perturbation of patient-derived cell line data, and finally in-vivo samples. Conclusions Overall, comboSC provides a feasible and one-stop computational prototype and a proof-of-concept study to predict potential drug combinations for further experimental validation and clinical usage using the single-cell transcriptome, which will facilitate and accelerate personalized tumor treatment by reducing screening time from a large drug combination space and saving valuable treatment time for individual patients. A user-friendly web server of comboSC for both clinical and research users is available at www.combosc.top. The source code is also available on GitHub at https://github.com/bm2-lab/comboSC.

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STNM1 in human cancers: role, function and potential therapy sensitizer

Cited by 4 publications

References 188 publications

Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Single-cell and spatial transcriptomics reveal a high glycolysis B cell and tumor-associated macrophages cluster correlated with poor prognosis and exhausted immune microenvironment in diffuse large B-cell lymphoma

Personalized tumor combination therapy optimization using the single-cell transcriptome

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