Kruppel-like factor 4 blocks tumor cell proliferation and promotes drug resistance in multiple myeloma

Schoenhals, Matthieu; Kassambara, Alboukadel; Veyrune, Jean-Luc; Moreaux, Jérôme; Goldschmidt, Hartmut; Hose, Dirk; Klein, Bernard

doi:10.3324/haematol.2012.066944

Cited by 25 publications

(27 citation statements)

References 46 publications

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“…Attenuation of KLF-4 expression promotes carcinogenesis by inducing G1/S phase arrest in clear cell renal cell carcinoma (Song et al, 2013). KLF-4 blocks tumor cell proliferation and promotes drug resistance in multiple myeloma (Schoenhals et al, 2013). In the present study, we investigated the regulatory role of KLF-4 in the proliferation of CRC HT-29 cells by abrogating KLF-4 expression.…”

Section: Discussionmentioning

confidence: 96%

Tumor-suppressive role of Kruppel-like factor 4 (KLF-4) in colorectal cancer

et al. 2017

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ABSTRACT. Kruppel-like factors (KLFs) are a group of transcriptional regulators that have recently been identified to exhibit tumorsuppressive function against various gastrointestinal cancers. The present study aims to investigate the expression patterns and prognostic value of KLF-4 in colorectal cancers (CRCs). KLF-4 levels in CRC tissues were examined via immunohistochemistry analysis, real-time quantitative polymerase chain reaction, and western blotting. The chisquare test was performed to evaluate the correlation between KLF-4 expression and the clinicopathological characteristics. Kaplan-Meier analysis was performed to assess the prognostic value of KLF-4 in CRC patients. In addition, we evaluated the effect of KLF-4 knockdown on the proliferation of CRC HT-29 cells. Our results showed significant downregulation of KLF-4 in 31 CRC samples, collected from CRC patients showing more malignant characteristics such as lymphatic metastasis, low tumor cell differentiation, and tumor recurrence. CRC patients in the low KLF-4 group were found to have reduced overall

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Section: Discussionmentioning

confidence: 96%

Tumor-suppressive role of Kruppel-like factor 4 (KLF-4) in colorectal cancer

et al. 2017

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“…Transducing in vitro generated PBs with a control measles lentivirus did not change EPC counts as previously indicated (results not shown). 18 This increase in EPC counts by a forced KLF4 expression is the result of combined increases in cell survival (from 48% in control EPCs to 65% in KLF4 C EPCs, P D .004, Fig. 2B) and in the efficacy of the differentiation of PBs into EPCs (from 49% CD138 C EPCs in the control group to 57% CD138 C EPCs in the KLF4 group, P D .02, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…20 Measles envelop pseudotyped lentiviruses were used because they can transduce human PCs unlike vsv-g envelop pseudotyped ones 18 (Fig. 1B).…”

Section: Resultsmentioning

confidence: 99%

“…High levels of KLF4 expression have been reported myeloma patients with t(4;14) translocation, an overexpression of CCND1 or CCND3. 18,32 Furthermore, KLF4 overexpression was described to be associated with melphalan and carfilzomib drug resistance in myeloma cells. 18,19 In conclusion, we have shown that KLF4 promotes the generation of human mature plasma cells in vitro, enhancing both the ability of plasmablasts to generate early and long lived plasma cells and the survival of plasma cells.…”

Section: Discussionmentioning

confidence: 99%

“…18 Furthermore, KLF4 was identified to play a role in Carfilzomib resistance through prosurvival autophagy induction in MM cells.…”

Section: Introductionmentioning

confidence: 99%

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Forced KLF4 expression increases the generation of mature plasma cells and uncovers a network linked with plasma cell stage

et al. 2016

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A role of the transcription factor Kr€ uppel-like factor 4 (KLF4) in the generation of mature plasma cells (PC) is unknown. Indeed, KLF4 is critical in controlling the differentiation of various cell linages, particularly monocytes and epithelial cells. KLF4 is expressed at low levels in pro-B cells and its expression increases as they mature into pre-B cells, resting na€ ıve B cells and memory B cells. We show here that KLF4 is expressed in human bone marrow plasma cells and its function was studied using an in vitro model of differentiation of memory B cells into long lived plasma cells. KLF4 is rapidly lost when memory B cells differentiate into highly cell cycling plasmablasts, poorly cycling early plasma cells and then quiescent long-lived plasma cells. A forced expression of KLF4 in plasmablasts enhances the yield of their differentiation into early plasma cell and long lived plasma cells, by inhibiting apoptosis and upregulating previously unknown plasma cell pathways.

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Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4

Park

Lewis

Chen

et al. 2019

Stem Cells Translational Medicine

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Pluripotent and tissue‐specific stem cells, such as blood‐forming stem cells, are maintained through a balance of quiescence, self‐renewal, and differentiation. Self‐renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self‐renewal, perhaps the most well‐known factors are members of the Krüppel‐like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells. Because KLF4 regulates gene expression through transcriptional activation or repression via either DNA binding or protein‐to‐protein interactions, the outcome of KLF4‐mediated regulation largely depends on the cellular context, cell cycle regulation, chromatin structure, and the presence of oncogenic drivers. This study first summarizes the current understanding of the regulation of self‐renewal by KLF proteins in embryonic stem cells through a KLF circuitry and then delves into the potential function of KLF4 in normal hematopoietic stem cells and its emerging role in leukemia‐initiating cells from pediatric patients with T‐cell acute lymphoblastic leukemia via repression of the mitogen‐activated protein kinase 7 pathway. stem cells translational medicine 2019;8:568–574

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Kruppel-like factor 4 blocks tumor cell proliferation and promotes drug resistance in multiple myeloma

Cited by 25 publications

References 46 publications

Tumor-suppressive role of Kruppel-like factor 4 (KLF-4) in colorectal cancer

Tumor-suppressive role of Kruppel-like factor 4 (KLF-4) in colorectal cancer

Forced KLF4 expression increases the generation of mature plasma cells and uncovers a network linked with plasma cell stage

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4

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