KLF4 Mediates the Effect of 5-ASA on the β-Catenin Pathway in Colon Cancer Cells

Parenti, Sandra; Montorsi, Lucia; Fantini, Sebastian; Mammoli, Fabiana; Gemelli, Claudia; Atene, Claudio Giacinto; Losi, Lorena; Frassineti, Chiara; Calabretta, Bruno; Tagliafico, Enrico; Ferrari, Sérgio; Zanocco-Marani, Tommaso; Grande, Alexis

doi:10.1158/1940-6207.capr-17-0382

Cited by 13 publications

(12 citation statements)

References 25 publications

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“…Nevertheless, KLF4 is important in regulating response to many known drugs [ 1 ]. These include cetuximab [ 23 ], cisplatin [ 19 , 43 , 72 , 84 , 102 ], gefitinib [ 79 ], glibenclamide [ 78 ], mesalazine [ 22 ] and Sijunzi decoction [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…The treatment with 5-ASA–induces µ-protocadherin expression, and KLF4 is a direct regulator of µ-protocadherin in this context. The underlying molecular mechanism involves miR-130a and miR-135b, as these microRNAs target KLF4 and 5-ASA treatment suppresses their expression [ 22 ]. KLF4 p.A472D mutation contributes to acquired resistance to cetuximab, a human-mouse chimeric IgG1 mAb that targets the extracellular domain of epidermal growth factor receptor (EGFR) and is effective in treating RAS wild-type and BRAF V600E wild-type patients with metastatic CRC [ 23 ].…”

Section: Colorectal Cancermentioning

confidence: 99%

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

Taracha-Wisniewska

Kotarba

Dworkin

et al. 2020

IJMS

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Krüppel-like factor 4 (KLF4) is a transcription factor highly conserved in evolution. It is particularly well known for its role in inducing pluripotent stem cells. In addition, KLF4 plays many roles in cancer. The results of most studies suggest that KLF4 is a tumor suppressor. However, the functioning of KLF4 is regulated at many levels. These include regulation of transcription, alternative splicing, miRNA, post-translational modifications, subcellular localization, protein stability and interactions with other molecules. Simple experiments aimed at assaying transcript levels or protein levels fail to address this complexity and thus may deliver misleading results. Tumor subtypes are also important; for example, in prostate cancer KLF4 is highly expressed in indolent tumors where it impedes tumor progression, while it is absent from aggressive prostate tumors. KLF4 is important in regulating response to many known drugs, and it also plays a role in tumor microenvironment. More and more information is available about upstream regulators, downstream targets and signaling pathways associated with the involvement of KLF4 in cancer. Furthermore, KLF4 performs critical function in the overall regulation of tissue homeostasis, cellular integrity, and progression towards malignancy. Here we summarize and analyze the latest findings concerning this fascinating transcription factor.

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Section: Discussionmentioning

confidence: 99%

Section: Colorectal Cancermentioning

confidence: 99%

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

Taracha-Wisniewska

Kotarba

Dworkin

et al. 2020

IJMS

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“…The evidence suggests that the interaction between Klf4 and β-catenin might be happening through the formation of a protein complex rather than via the transcriptional regulation in the pancreatic CTC-S group. Even though there are studies claiming that Klf4 inhibits β-catenin [74][75][76], there are other reports showing that the Klf4 / β-catenin complex is necessary for the self-renewal capacity of stem/cancer cells [68]. The consensus is that the protein-protein interaction between Klf4 and β-catenin happens in the nucleus [68,[74][75][76].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Stem-like Circulating Tumor Cells in Pancreatic Cancer

et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) is the fourth most frequent cause of death from cancer. Circulating tumor cells (CTCs) with stem-like characteristics lead to distant metastases and thus contribute to the dismal prognosis of PDAC. Our purpose is to investigate the role of stemness in CTCs derived from a genetically engineered mouse model of PDAC and to further explore the potential molecular mechanisms. The publically available RNA sequencing dataset GSE51372 was analyzed, and CTCs with (CTC-S) or without (CTC-N) stem-like features were discriminated based on a principal component analysis (PCA). Differentially expressed genes, weighted gene co-expression network analysis (WGCNA), and further functional enrichment analyses were performed. The prognostic role of the candidate gene (CTNNB1) was assessed in a clinical PDAC patient cohort. Overexpression of the pluripotency marker Klf4 (Krüppel-like factor 4) in CTC-S cells positively correlates with Ctnnb1 (β-Catenin) expression, and their interaction presumably happens via protein–protein binding in the nucleus. As a result, the adherens junction pathway is significantly enriched in CTC-S. Furthermore, the overexpression of Ctnnb1 is a negative prognostic factor for progression-free survival (PFS) and relapse-free survival (RFS) in human PDAC cohort. Overexpression of Ctnnb1 may thus promote the metastatic capabilities of CTCs with stem-like properties via adherens junctions in murine PDAC.

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“…miR-130a was a potential therapeutic target of CRC. miR-130a functioned as a radiosensitizer in rectal cancer [48], and curcumin and mesalazine suppressed the colon cancer proliferation by inhibiting the expression of miR-130a [49,50]. To our knowledge, this study is the rst to clarify the speci c expression of miR-561 and miR-4684 in the tumors & serums of CRC patients and to identify their prognostic and diagnostic capacity in CRC.…”

Section: Function Of the Four Mirnasmentioning

confidence: 99%

A Novel Four-MicroRNA Signature for Prognosis and Diagnosis in Colorectal Cancer

Chen

Qin

Zhou

et al. 2020

Preprint

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Background and aims: Colorectal cancer (CRC) remains a global public health problem. We aimed to access prognostic microRNAs (miRNAs) associated with overall survival (OS) and evaluate their diagnostic value in CRC.Methods: Three serum miRNA expression profiles from Gene Expression Omnibus (GEO) database and tissue miRNA expression profile of CRC from The Cancer Genome Atlas (TCGA) database were studied to get common differentially expressed miRNA (DEmiRNAs) in serums and tissues. 569 CRC patients with survival information from TCGA database were randomly divided into the discovery and validation cohort. Based on the TCGA discovery cohort, the univariate cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate cox proportional hazards regression analysis were performed and a prognostic signature was constructed. The prognostic capacity of the signature was verified in TCGA validation cohort and the prognostic signature expression in tumors and serums was validated in an independent microarray dataset and our clinical set. We also evaluated the diagnostic power of the model in serum by calculating the area under the receiver operating characteristic (ROC) curve in a clinical set. Functional enrichment analyses were applied to analyze the potential roles of the signature in CRC.Results: A total of 154 common DEmiRNAs were identified. Based on the TCGA discovery cohort, a four-miRNA (miR-10b, miR-130a, miR-561, miR-4684) prognostic signature was constructed and a predictive nomogram model including the expression of above four miRNAs showed good performance for predicting the 3- and 5-year overall survival. The findings were well verified in TCGA validation cohort. miR-10b, miR-130a, miR-561 and miR-4684 were significantly upregulated both in CRC tumors and serums. Circulating miR-10b, miR-130a, miR-561 and miR-4684 levels were significantly downregulated after surgical resection of tumor in CRC patients, suggesting these four circulating miRNAs in the serum were tumor derived. The four circulating miRNA combination might act as a novel diagnostic signature for CRC. Functional enrichment analyses suggested that above four miRNAs might be related to the progression of CRC. Conclusions: We developed a novel reliable prognostic and diagnostic signature, which should be beneficial for CRC screening and clinical therapeutic decision-making.

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KLF4 Mediates the Effect of 5-ASA on the β-Catenin Pathway in Colon Cancer Cells

Cited by 13 publications

References 25 publications

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

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

Characterization of Stem-like Circulating Tumor Cells in Pancreatic Cancer

A Novel Four-MicroRNA Signature for Prognosis and Diagnosis in Colorectal Cancer

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