Targeting FoxM1 by thiostrepton inhibits growth and induces apoptosis of laryngeal squamous cell carcinoma

Jiang, Li; Wu, Xiaosong; Wang, Peng; Wen, Taoyu; Yu, Chao; Chen, Hongyan

doi:10.1007/s00432-014-1872-3

Cited by 38 publications

(29 citation statements)

References 30 publications

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“…Targeting FoxM1 may have promising therapeutic benefits for cancer treatment [35]. Thiostrepton (TST), a specific inhibitor for FoxM1, shows anti-cancer activity in many human cancers [19][20][21][22]. In the current study, primary CRC cells with higher level of TRIM6 was more sensitive to TST (Fig.…”

Section: Discussionmentioning

confidence: 54%

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TRIM6 promotes colorectal cancer cells proliferation and response to thiostrepton by TIS21/FoxM1

Zheng

Zhou

Wang

et al. 2020

J Exp Clin Cancer Res

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Background: Tripartite motif-containing proteins (TRIM) play a crucial role in carcinogenesis. Little attention has been focused on the possible functions of TRIM6 on carcinogenesis. Methods: The expression levels of TRIM6 were assessed in colorectal cancer (CRC) samples. TRIM6 expression was knocked down in CRC cell lines, and subjected to Cell counting kit-8 (CCK-8), bromodeoxyuridine (BrdU) incorporation and cell cycle assays. Immunoprecipitation and proteomics analysis was performed to identify potential associated proteins of TRIM6. Results: TRIM6 expression was up-regulated in CRC samples and TRIM6 expression may be an independent prognostic marker for CRC. Knocking down TRIM6 expression suppressed CRC cell proliferation, induced cell cycle arrested at G2/M phase and increased sensitivity to 5-fluorouracil and oxaliplatin. TIS21, an anti-proliferative protein involved in the regulation of G2/M arrest, was identified as an interaction partner of TRIM6. Moreover, CRC cells with TRIM6 overexpression showed decreased TIS21 protein stability. TIS21 ubiquitination was increased in CRC cells overexpressing TRIM6, but not in those overexpressing TRIM6 E3 catalytic mutant (C15A). Further, Lys5 was essential for TRIM6 mediated TIS21 ubiquitination. TIS21 overexpression reversed the induced effects of TRIM6 overexpression on CRC cell proliferation, and the levels of forkhead box M1 (FoxM1), phosphorylated FoxM1, Cyclin B1 and c-Myc. Thiostrepton, a specific inhibitor for FoxM1, was less effective in anti-proliferative activity against CRC cells with lower level of TRIM6 in vitro and in vivo. Conclusions: Our study suggests that TRIM6 promotes the progression of CRC via TIS21/FoxM1.

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Section: Discussionmentioning

confidence: 54%

“…In vitro and in vivo experiments have supported the anti-cancer activity of FoxM1 inhibitor thiostrepton (TST) [19][20][21][22]. Given the positive correlation between TRIM6 and FoxM1 in CRC, we present a hypothesis that TRIM6 expression level influences the effect of TST on CRC cells.…”

Section: Trim6 Expression Level Influenced the Anti-proliferative Effmentioning

confidence: 90%

TRIM6 promotes colorectal cancer cells proliferation and response to thiostrepton by TIS21/FoxM1

Zheng

Zhou

Wang

et al. 2020

J Exp Clin Cancer Res

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“…Over-expression of XIAP is found in most cancer cells, and it correlates with tumor progression, poor prognosis and drug resistance [35,36]. The abnormal activation of cell proliferation and apoptosis inhibition are found in many cancers, including laryngeal cancer [37].…”

Section: Discussionmentioning

confidence: 99%

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells

Tian

Tao

et al. 2018

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The early-stage diagnosis and treatment for the recurrence of larynx carcinoma needs further investigation. Mesenchyme homeobox 2 (MEOX2) was speculated as a novel suppressor gene in larynx carcinoma in our study, the molecular mechanism was studied. Real-time quantitative PCR (RT-qPCR) and Western blot were used to detect mRNA and protein levels of MEOX2 in laryngeal cancer tissues and cells (Hep-2, TU212, AMC-NH-8 and TU686 cells), and also apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase (Akt) related factors in TU212 cells transfected with MEOX2. Cell counting kit-8 (CCK8) assay and Annexin-Ⅴ/PI staining assay were conducted to determine cell viability and apoptosis rates respectively.46 patients with larynx carcinoma were involved in this study. The expression of MEOX2 was lower in larynx carcinoma tissues than normal tissues, correlated with clinical stages, differentiated degrees, and survival times. The expression of MEOX2 was the lowest among those laryngeal cancer cells, and was chosen to be transfected with MEOX2 in the following study. Over-expression of MEOX2 inhibited cell viability and promoted apoptosis of TU212 cells, via increasing the expression levels of Caspase-3, and decreasing levels of C-Myc, XIAP, PI3K p110α, PI3K p110β, PI3K class III and p-Akt. In summary, the expression levels of MEOX2 were inhibited in larynx carcinoma than normal tissues, correlated with the progression of the cancer. Over-expression of MEOX2 in laryngeal cancer cells inhibited cell viability and promoted apoptosis, via regulating apoptosis and PI3K/Akt pathway related factors. It would provide evidence for MEOX2 to be used as a therapeutical gene in larynx carcinoma.

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“…By positively regulating oncogenes such as VEGF and B-cell lymphoma 2 (BCL-2) (Karadedou et al, 2012;Liu et al, 2017b), FOXM1 impacts tumor initiation, angiogenesis, progression, drug resistance, and metastasis in prostate cancer, hepatocellular carcinoma, pancreatic cancer, colon cancer, breast cancer, and glioblastoma (Bella et al, 2014). Thus, FOXM1 inhibition has been suggested as an antitumor strategy (Hegde et al, 2011;Jiang et al, 2015;Ju et al, 2015;Wang and Gartel, 2011;Zhang et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Epigenetically modulated FOXM1 suppresses dendritic cell maturation in pancreatic cancer and colon cancer

et al. 2019

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Forkhead box transcription factor M1 ( FOXM 1) is a proliferation‐associated transcription factor involved in tumorigenesis through transcriptional regulation of its target genes in various cells, including dendritic cells ( DC s). Although previous work has shown that FOXM 1 enhances DC maturation in response to house dust mite allergens, it is not known whether FOXM 1 affects DC maturation in the context of tumor‐specific immunity. In this study, we examined the central role of FOXM 1 in regulating bone marrow‐derived dendritic cell ( BMDC ) maturation phenotypes and function in pancreatic cancer and colon cancer. FOXM 1 retarded maturation phenotypes of BMDC s, inhibited promotion of T‐cell proliferation, and decreased interleukin‐12 ( IL ‐12) p70 in tumor‐bearing mice ( TBM ). Notably, FOXM 1 expression was epigenetically regulated by dimethylation on H3 lysine 79 (H3K79me2), a modification present in both tumor cells and BMDC s. Increased H3K79me2 enrichment was observed at the FOXM 1 promoter in both BMDC s from TBM , and in BMDC s from wild‐type mice cultured with tumor‐conditioned medium that mimics the tumor microenvironment ( TME ). Furthermore, inhibition of the H3K79 methyltransferase DOT 1L not only decreased enrichment of H3K79me2, but also downregulated expression of FOXM 1 and partially reversed its immunosuppressive effects on BMDC s. Furthermore, we found that FOXM 1 upregulated transcription of Wnt family number 5A (Wnt5a) in BMDC s in vitro ; we also observed that exogenous Wnt5a expression abrogated BMDC maturation phenotypes by inhibiting FOXM 1 and H3K79me2 modification. Therefore, our results reveal that upregulation of FOXM 1 by H3K79me2 in pancreatic cancer and colon cancer significantly inhibits maturation phenotypes and function of BMDC s through the Wnt5a signaling pathway, and thus provide novel insights into FOXM 1‐based antitumor immunotherapy.

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Targeting FoxM1 by thiostrepton inhibits growth and induces apoptosis of laryngeal squamous cell carcinoma

Cited by 38 publications

References 30 publications

TRIM6 promotes colorectal cancer cells proliferation and response to thiostrepton by TIS21/FoxM1

TRIM6 promotes colorectal cancer cells proliferation and response to thiostrepton by TIS21/FoxM1

Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells

Epigenetically modulated FOXM1 suppresses dendritic cell maturation in pancreatic cancer and colon cancer

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