FOXM1: A small fox that makes more tracks for cancer progression and metastasis

Khan, Md Arafat; Κhan, Parvez; Ahmad, Aatiya; Fatima, Mahek; Nasser, Mohd W.

doi:10.1016/j.semcancer.2023.03.007

Cited by 40 publications

(24 citation statements)

References 213 publications

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“…While the patterns of the regulated TFs were context-dependent, it is also of interest that several were regulated in three different lines. Among them was downregulated FOXM1, a well-studied oncogenic TF with a variety of roles in promoting cancers [59,60], including through the stimulation of cell cycle progression. The regulation of many TFs by Dpep suggested the idea that the peptide triggers a cascade of context-dependent TF activity that ultimately leads to the activation of apoptotic pathways.…”

Section: Discussionmentioning

confidence: 99%

Dpep Inhibits Cancer Cell Growth and Survival via Shared and Context-Dependent Transcriptome Perturbations

Zhou,

Greene

2023

Cancers

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Dpep is a cell-penetrating peptide targeting transcription factors ATF5, CEBPB, and CEBPD, and that selectively promotes the apoptotic death of multiple tumor cell types in vitro and in vivo. As such, it is a potential therapeutic. To better understand its mechanism of action, we used PLATE-seq to compare the transcriptomes of six cancer cell lines of diverse origins before and after Dpep exposure. This revealed a context-dependent pattern of regulated genes that was unique to each line, but that exhibited a number of elements that were shared with other lines. This included the upregulation of pro-apoptotic genes and tumor suppressors as well as the enrichment of genes associated with responses to hypoxia and interferons. Downregulated transcripts included oncogenes and dependency genes, as well as enriched genes associated with different phases of the cell cycle and with DNA repair. In each case, such changes have the potential to lie upstream of apoptotic cell death. We also detected the regulation of unique as well as shared sets of transcription factors in each line, suggesting that Dpep may initiate a cascade of transcriptional responses that culminate in cancer cell death. Such death thus appears to reflect context-dependent, yet shared, disruption of multiple cellular pathways as well as of individual survival-relevant genes.

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Section: Discussionmentioning

confidence: 99%

Dpep Inhibits Cancer Cell Growth and Survival via Shared and Context-Dependent Transcriptome Perturbations

Zhou,

Greene

2023

Cancers

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“…7A ). FOXM1 is an important cell cycle regulator overexpressed in many cancers [ 22 , 23 ]. It regulates the expression of genes required for G2/M transition and is essential for mitotic entry and progression [ 24 , 25 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

“…iRegulon analysis identified the oncogenic transcription factor FOXM1 as a key regulatory molecule in colorectal cancer growth. FOXM1 is overexpressed in various human cancers and is implicated in several cancer processes, such as proliferation, metastasis, and therapeutic resistance [ 22 , 23 , 43 , 44 , 45 ]. Inhibition of FOXM1 is expected to sensitize cancer cells to conventional chemotherapy [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Peptide mimetic NC114 induces growth arrest by preventing PKCδ activation and FOXM1 nuclear translocation in colorectal cancer cells

Taguchi,

Nakaya,

Aizawa

et al. 2024

FEBS Open Bio

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The peptide mimetic, NC114, is a promising anticancer compound that specifically kills colorectal cancer cells without affecting normal colon epithelial cells. In our previous study, we observed that NC114 inhibited the Wnt/β‐catenin pathway, with significant downregulation of both Ser 675‐phosphorylated β‐catenin and its target genes, cyclin D1 and survivin. However, the molecular mechanism responsible for its cytotoxic effect has not yet been fully characterized. In the present study, we demonstrated that NC114 prevented cell cycle progression from S to G2/M phase by downregulating cell cycle‐related gene expression, and also induced growth arrest in SW480 and HCT‐116 colorectal cancer cells. A novel covariation network analysis combined with transcriptome analysis revealed a series of signaling cascades affected by NC114 treatment, and identified protein kinase C‐δ (PKCδ) and forkhead box protein M1 (FOXM1) as important regulatory factors for NC114‐induced growth arrest. NC114 treatment inhibits the activation of PKCδ and its kinase activity, which suppresses MEK/ERK signaling. Attenuated MEK/ERK signaling then results in a reduction in FOXM1 phosphorylation and subsequent nuclear translocation of FOXM1 and β‐catenin. Consequently, formation of a T‐cell factor‐4 (TCF4)/β‐catenin transcription complex in the nucleus is inhibited and transcription of its target genes, such as cell cycle‐related genes, is downregulated. The efficacy of NC114 on tumor growth was confirmed in a xenograft model. Collectively, elucidation of the mechanism by which NC114 induces growth arrest in colorectal cancer cells should provide a novel therapeutic strategy for colorectal cancer treatment.

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“…Six genes— FOXM1 , F2RL1 , PRKCD , CLEC7A , PDGFB , and RAC1 — were pinpointed as critical components of the predictive signature. Specifically, FOXM1 's upregulation and amplification are implicated in various cancers, including NSCLC, contributing to processes such as invasion, movement, new blood vessel formation, cellular differentiation, and resistance to treatments 59 . Past research has indicated that the phosphorylation of FOXM1 at Ser25 can activate genes like IL1A/B, VEGFA, and IL6, which in turn can attract monocytes and promote the differentiation of tumor-associated macrophages (TAMs) towards an M2-like phenotype, thereby aiding in immune escape and fostering an immunosuppressive TME 60 .…”

Section: Discussionmentioning

confidence: 99%

Discovery of a novel ROS-based signature for predicting prognosis and immunosuppressive tumor microenvironment in lung adenocarcinoma

Guo,

Chang,

Wan

et al. 2024

J. Cancer

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The role of reactive oxygen species (ROS) is critical in the emergence and progression of lung adenocarcinoma (LUAD), affecting cell survival, proliferation, angiogenesis, and metastasis. Further investigations are needed to elucidate these effects' precise pathways and devise therapeutic approaches targeting ROS. Moreover, the expression pattern and clinical significance of the ROS-related genes in LUAD remain elusive. Through comprehensive analysis incorporating 1494 LUAD cases from The Cancer Genome Atlas, six Gene Expression Omnibus series, and a Chinese LUAD cohort, we identified a ROS-related signature with substantial predictive value in various LUAD patient cohorts. The ROS-related signature has demonstrated a significant negative relationship with antitumor immunity and dendritic cell maturation and activation. Moreover, The ROS-related signature showed predictive value on immunotherapy outcomes across multiple types of solid tumors, including LUAD. These findings reinforce the ROS-related signature as a predictive tool for LUAD and provide new insights into its link with antitumor immunity and immunotherapy efficacy. These results have implications for refining clinical assessments and tailoring immunotherapeutic strategies for patients with LUAD.

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FOXM1: A small fox that makes more tracks for cancer progression and metastasis

Cited by 40 publications

References 213 publications

Dpep Inhibits Cancer Cell Growth and Survival via Shared and Context-Dependent Transcriptome Perturbations

Dpep Inhibits Cancer Cell Growth and Survival via Shared and Context-Dependent Transcriptome Perturbations

Peptide mimetic NC114 induces growth arrest by preventing PKCδ activation and FOXM1 nuclear translocation in colorectal cancer cells

Discovery of a novel ROS-based signature for predicting prognosis and immunosuppressive tumor microenvironment in lung adenocarcinoma

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