KLF4 induces Mesenchymal - Epithelial Transition (MET) by suppressing multiple EMT-inducing transcription factors

Subbalakshmi, Ayalur Raghu; Sahoo, Sarthak; McMullen, Isabelle; Saxena, Aaditya Narayan; Venugopal, S.; Somarelli, Jason A.; Jolly, Mohit Kumar

doi:10.1101/2021.08.26.457621

Cited by 6 publications

(1 citation statement)

References 95 publications

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“…The miRNA‐135b reduces the expression level of CAMK2D to induce EMT and increase metastasis of gastric cancer cells (Huangfu et al, 2021). Overall, different studies have described novel pathways that can regulate EMT by distinct mechanisms in cancer cells (C. Imbroisi Filho et al, 2021; C. Li et al, 2021; X. Meng et al, 2021; Subbalakshmi et al, 2021) and the focus of current study is to evaluate the role of NF‐κB signaling in regulating EMT in various cancers. Figure 2 provides a schematic representation of the EMT process.…”

Section: Emt Mechanismmentioning

confidence: 99%

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Mirzaei

Saghari

Bassiri

et al. 2022

Journal Cellular Physiology

118

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Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival and prognosis of cancer patients. The epithelial‐to‐mesenchymal transition (EMT) is a well‐known mechanism responsible for the invasiveness of tumor cells. A number of molecular pathways can regulate the EMT mechanism in cancer cells and nuclear factor‐kappaB (NF‐κB) is one of them. The nuclear translocation of NF‐κB p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF‐κB and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF‐κB signaling, its activation enhances metastasis of tumor cells via EMT induction. This has been confirmed in various cancers including brain, breast, lung and gastric cancers, among others. The ZEB1/2, transforming growth factor‐β, and Slug as inducers of EMT undergo upregulation by NF‐κB to promote metastasis of tumor cells. After EMT induction driven by NF‐κB, a significant decrease occurs in E‐cadherin levels, while N‐cadherin and vimentin levels undergo an increase. The noncoding RNAs can potentially also function as upstream mediators and modulate NF‐κB/EMT axis in cancers. Moreover, NF‐κB/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF‐κB/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents.

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Section: Emt Mechanismmentioning

confidence: 99%

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Mirzaei

Saghari

Bassiri

et al. 2022

Journal Cellular Physiology

118

View full text Add to dashboard Cite

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Interplay between Partial EMT and Cisplatin Resistance as the Drivers for Recurrence in HNSCC

Ingruber

Dudás

Sprung³

et al. 2022

Biomedicines

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This study aims to investigate the role of partial epithelial to mesenchymal transition (pEMT)-related proteins in modulating Cisplatin resistance in head and neck squamous cell carcinoma (HNSCC). SCC-25 cells were pre-treated with TGF-beta1 followed by transient Krüppel-like Factor 4 (KLF4)-overexpression and Cisplatin treatment. Cell growth, cell morphological changes and cell migration were assessed using Juli BR live cell video-microscopy. In addition, Ki-67 and Slug immunostaining and follow-up image cytometric analysis of primary and recurrent HNSCC tumors were performed to evaluate the proliferation index (PI) and the EMT-like phenotype. We observed that proliferating and Slug-positive tumor cells expand after therapy in HNSCC. Subsequently, protein analysis revealed the stabilization of Slug, upregulation of Vimentin and phospho-p38 (p-p38) in Cisplatin-resistant SCC-25 cells. Moreover, KLF4-overexpression contributed to Cisplatin sensitivity by reduction of Slug at the protein level. This work strongly suggests that an pEMT-like pathway is activated in recurrent and Cisplatin-resistant HNSCC. Finally, stable KLF4-overexpression might sensitize HNSCC tumor cells for Cisplatin treatment.

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Characterization of Accessible Chromatin Regions in Cattle Rumen Epithelial Tissue during Weaning

Boschiero

Gao

Baldwin

et al. 2022

Genes

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Weaning in ruminants is characterized by the transition from a milk-based diet to a solid diet, which drives a critical gastrointestinal tract transformation. Understanding the regulatory control of this transformation during weaning can help to identify strategies to improve rumen health. This study aimed to identify regions of accessible chromatin in rumen epithelial tissue in pre- and post-weaning calves and investigate differentially accessible regions (DARs) to uncover regulatory elements in cattle rumen development using the ATAC-seq approach. A total of 126,071 peaks were identified, covering 1.15% of the cattle genome. From these accessible regions, 2766 DARs were discovered. Gene ontology enrichment resulted in GO terms related to the cell adhesion, anchoring junction, growth, cell migration, motility, and morphogenesis. In addition, putative regulatory canonical pathways were identified (TGFβ, integrin-linked kinase, integrin signaling, and regulation of the epithelial–mesenchymal transition). Canonical pathways integrated with co-expression results showed that TGFβ and ILK signaling pathways play essential roles in rumen development through the regulation of cellular adhesions. In this study, DARs during weaning were identified, revealing enhancers, transcription factors, and candidate target genes that represent potential biomarkers for the bovine rumen development, which will serve as a molecular tool for rumen development studies.

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KLF4 induces Mesenchymal - Epithelial Transition (MET) by suppressing multiple EMT-inducing transcription factors

Cited by 6 publications

References 95 publications

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Interplay between Partial EMT and Cisplatin Resistance as the Drivers for Recurrence in HNSCC

Characterization of Accessible Chromatin Regions in Cattle Rumen Epithelial Tissue during Weaning

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