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

Schoenhals, Matthieu; Jourdan, Michel; Seckinger, Anja; Pantesco, Véronique; Hose, Dirk; Kassambara, Alboukadel; Moreaux, Jérôme; Klein, Bernard

doi:10.1080/15384101.2016.1191709

Cited by 10 publications

(8 citation statements)

References 39 publications

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“…Gefitinib can induce apoptosis by activating the caspase cascade in NSCLC cells carrying the sensitive mutation of EGFR . Krüppel‐like factor 4 also has an ambiguous apoptosis‐induced effect in bladder cancer cells, breast cancer cells, and plasma cells . The present study revealed that knockdown of KLF4 promoted gefitinib‐induced apoptosis by upregulating expression of apoptosis‐related proteins in c‐Met‐overexpressing NSCLC cells (Figure A,C) but not in NSCLC cells without c‐Met overexpression (Figure ), whereas overexpression of KLF4 suppressed gefitinib‐induced apoptosis in gefitinib‐sensitive cells (Figure B,D).…”

Section: Discussionmentioning

confidence: 48%

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

et al. 2018

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Gefitinib has been widely used in the first‐line treatment of advanced EGFR‐mutated non‐small‐cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9‐14 months of treatment. This study revealed that Krüppel‐like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c‐Met‐overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c‐Met‐overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib‐resistant NSCLC cell lines without c‐Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib‐resistant NSCLC cells with c‐Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib‐sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c‐Met‐overexpressing NSCLC cells by inhibiting the expression of apoptosis‐related proteins under gefitinib treatment and activating the c‐Met/Akt signaling pathway by decreasing the inhibition of β‐catenin on phosphorylation of c‐Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c‐Met overexpression.

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Section: Discussionmentioning

confidence: 48%

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

et al. 2018

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“…It was recently shown that KLF4 enhances memory B-cells differentiation into early plasma cell and long lived plasma cells (111–113). …”

Section: Physiological Functions In Tissues and Organsmentioning

confidence: 99%

Krüppel-like factor 4 (KLF4): What we currently know

Ghaleb

Yang

2017

Gene

428

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Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger-containing transcription factor that regulates diverse cellular processes such as cell growth, proliferation, and differentiation. Since its discovery in 1996, KLF4 has been gaining a lot of attention, after it was shown in 2006 as one of four factors required for the induction of pluripotent stem cells (iPSCs). Here we review the current knowledge on the different functions and roles of KLF4 in various tissue and organ systems.

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“…This hypoxic microenvironment is important for normal bone marrow hematopoiesis. We investigated the impact of decreased oxygen partial pressures in plasma cell generation using our in vitro model 3,6,11,12 at each step (day 4, day 7 and day 10) of B cell differentiation (Fig. 1A).…”

Section: Introductionmentioning

confidence: 99%

Hypoxia favors the generation of human plasma cells

et al. 2017

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Plasma cells (PCs) generation occurs in hypoxic conditions in vivo, whereas the relevance of O 2 pressure in PC differentiation remains unknown.Using our in vitro PC differentiation model, we investigated the role of hypoxia in PC generation. Hypoxia increases the generation of plasmablasts (PBs) starting from memory B cells, by increasing cell cycle and division number. Reactome analysis demonstrated a significant enrichment of genes involved in HIF1a and HIF2a transcription factor network, metabolism and MYC related pathways in hypoxic compared with normoxic PBs. Hypoxia-induced metabolism alteration and MYC pathway are involved in malignant PC pathophysiology. Therefore, the expression of 28 out of the 74 genes overexpressed in hypoxic PBs compared with normoxic ones was found to be associated with an adverse prognosis (event free survival and overall survival) in newly diagnosed multiple myeloma patients.According to the role of hypoxia in supporting PBs generation through cell cycle induction, c-MYC activation and metabolism alteration, it could be involved in plasma cell tumorigenesis.

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

Cited by 10 publications

References 39 publications

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

Krüppel-like factor 4 (KLF4): What we currently know

Hypoxia favors the generation of human plasma cells

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