Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

Taracha-Wisniewska, Agnieszka; Kotarba, Grzegorz; Dworkin, Sebastian; Wilanowski, Tomasz

doi:10.3390/ijms21228843

Cited by 31 publications

(26 citation statements)

References 167 publications

(264 reference statements)

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“…Previous reports showed that KLF4, a zinc finger-type transcription factor, played a pivotal and different role in the development of various cancers, including lung cancer, HCC, and pancreatic cancer [ 44 – 48 ]. However, low expression of KLF4 promoted the growth, invasion, and metastasis of NSCLC, but high expression of KLF4 displayed a valuable role for therapy of NSCLC [ 49 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

Deguelin Attenuates Non-Small-Cell Lung Cancer Cell Metastasis by Upregulating PTEN/KLF4/EMT Signaling Pathway

et al. 2022

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Non-small-cell lung cancer (NSCLC) is the most common lung cancer and a major cause of cancer mortality worldwide. Deguelin plays a vital inhibitory role in NSCLC initiation and development. However, the downstream mechanism of deguelin-suppressed metastasis of NSCLC cells is still not completely understood. Interestingly, phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and Krüppel-like factor 4 (KLF4) also contribute to inhibition of metastasis in NSCLC cells. Here, we demonstrated that deguelin significantly upregulated PTEN and KLF4 expressions and PTEN positively upregulated KLF4 expression in NSCLC cells including A549 and PC9 cells. Moreover, overexpressions of PTEN and KLF4 inhibited the migration and invasion of NSCLC cells, an effect similar to that of deguelin. Furthermore, overexpressions of PTEN and KLF4 could suppress the epithelial-mesenchymal transition (EMT), an effect also similar to that of deguelin. Additionally, deguelin displayed a significant antitumor ability by upregulating PTEN and KLF4 expressions in mice model with NSCLC cells. Together, these results indicated that deguelin could be a potential therapeutic agent through upregulating PTEN and KLF4 expressions for NSCLC therapy.

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Section: Discussionmentioning

confidence: 99%

Deguelin Attenuates Non-Small-Cell Lung Cancer Cell Metastasis by Upregulating PTEN/KLF4/EMT Signaling Pathway

et al. 2022

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“…Krüppel-like factor 4 (KLF4) can inhibit the development of tumor by associating with the non-Warburg metabolic behaviors (Blum et al, 2021). Low expression of KLF4 may lead to poor prognosis and link to the progression of COAD (Taracha-Wisniewska et al, 2020). T-cell factor 7-like 1 (TCF7L1) has been found to have a high expression in many cancers, such as breast cancer and skin squamous cell carcinoma (Slyper et al, 2012;Ku et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Identification of Transcription Factor-Related Gene Signature and Risk Score Model for Colon Adenocarcinoma

Lin

Cao

et al. 2021

Front. Genet.

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The prognosis of colon adenocarcinoma (COAD) remains poor. However, the specific and sensitive biomarkers for diagnosis and prognosis of COAD are absent. Transcription factors (TFs) are involved in many biological processes in cells. As the molecule of the signal pathway of the terminal effectors, TFs play important roles in tumorigenesis and development. A growing body of research suggests that aberrant TFs contribute to the development of COAD, as well as to its clinicopathological features and prognosis. In consequence, a few studies have investigated the relationship between the TF-related risk model and the prognosis of COAD. Therefore, in this article, we hope to develop a prognostic risk model based on TFs to predict the prognosis of patients with COAD. The mRNA transcription data and corresponding clinical data were downloaded from TCGA and GEO. Then, 141 differentially expressed genes, validated by the GEPIA2 database, were identified by differential expression analysis between normal and tumor samples. Univariate, multivariate and Lasso Cox regression analysis were performed to identify seven prognostic genes (E2F3, ETS2, HLF, HSF4, KLF4, MEIS2, and TCF7L1). The Kaplan–Meier curve and the receiver operating characteristic curve (ROC, 1-year AUC: 0.723, 3-year AUC: 0.775, 5-year AUC: 0.786) showed that our model could be used to predict the prognosis of patients with COAD. Multivariate Cox analysis also reported that the risk model is an independent prognostic factor of COAD. The external cohort (GSE17536 and GSE39582) was used to validate our risk model, which indicated that our risk model may be a reliable predictive model for COAD patients. Finally, based on the model and the clinicopathological factors, we constructed a nomogram with a C-index of 0.802. In conclusion, we emphasize the clinical significance of TFs in COAD and construct a prognostic model of TFs, which could provide a novel and reliable model for the prognosis of COAD.

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“…KLF4 is a stem cell factor which, together with octamer-binding transcription factor 4, SOX2, homeobox protein NANOG and transcription factor MYC, is involved in the induction of pluripotent stem cells (97). Most studies suggest that KLF4 acts as a tumor suppressor, but protumorigenic activity of KLF4 has also been reported (98). KLF4 promoted ESCC differentiation by up-regulation of keratin 13 expression (99).…”

Section: Mirs Targeting Transcription Factorsmentioning

confidence: 99%

MicroRNAs and Corresponding Targets in Esophageal Cancer as ShownIn VitroandIn Vivoin Preclinical Models

Weidle

Nopora

2022

Cancer Genomics Proteomics

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Squamous cell carcinoma of the esophagus is associated with a dismal prognosis. Therefore, identification of new targets and implementation of new treatment modalities are issues of paramount importance. Based on a survey of the literature, we identified microRNAs conferring antitumoral activity in preclinical in vivo experiments. In the category of miRs targeting secreted factors and transmembrane receptors, four miRs were up-regulated and 10 were down-regulated compared with five out of nine in the category transcription factors, and six miRs were down-regulated in the category enzymes, including metabolic enzymes. The down-regulated miRs have targets which can be inhibited by small molecules or antibody-related entities, or re-expressed by reconstitution therapy. Up-regulated miRs have targets which can be reconstituted with small molecules or inhibited with antagomirs.

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Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types

Cited by 31 publications

References 167 publications

Deguelin Attenuates Non-Small-Cell Lung Cancer Cell Metastasis by Upregulating PTEN/KLF4/EMT Signaling Pathway

Deguelin Attenuates Non-Small-Cell Lung Cancer Cell Metastasis by Upregulating PTEN/KLF4/EMT Signaling Pathway

Identification of Transcription Factor-Related Gene Signature and Risk Score Model for Colon Adenocarcinoma

MicroRNAs and Corresponding Targets in Esophageal Cancer as ShownIn VitroandIn Vivoin Preclinical Models

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