Leptin stimulates <i>IGF</i>-1 transcription by activating AP-1 in human breast cancer cells

Min, Dong Yeong; Jung, Euitaek; Kim, Juhwan; Lee, Young Han; Shin, Soon Young

doi:10.5483/bmbrep.2019.52.6.189

Cited by 22 publications

(17 citation statements)

References 35 publications

(38 reference statements)

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“…Leptin functions are strengthened through cross talk with other different signaling molecules, including estrogen receptor α (ERα) [ 19 ], growth factors [ 20 , 21 ], inflammatory cytokines [ 22 ], and Notch [ 23 , 24 , 25 , 26 , 61 ].…”

Section: Discussionmentioning

confidence: 99%

“…Leptin is able to modulate the hallmarks of cancer development and progression, also through a functional interplay with other important molecular effectors, including estrogens, growth factors, and inflammatory cytokines [ 17 , 18 , 19 , 20 , 21 , 22 ]. In this context, the crosstalk between leptin and Notch pathways has been described in breast [ 23 , 24 ], pancreatic [ 25 ], and endometrial [ 26 ] cancers, where it affects cell proliferation, migration, invasion, angiogenesis, and chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

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Leptin and Notch Signaling Cooperate in Sustaining Glioblastoma Multiforme Progression

et al. 2020

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Glioblastoma multiforme (GBM) is the most malignant form of glioma, which represents one of the commonly occurring tumors of the central nervous system. Despite the continuous development of new clinical therapies against this malignancy, it still remains a deadly disease with very poor prognosis. Here, we demonstrated the existence of a biologically active interaction between leptin and Notch signaling pathways that sustains GBM development and progression. We found that the expression of leptin and its receptors was significantly higher in human glioblastoma cells, U-87 MG and T98G, than in a normal human glial cell line, SVG p12, and that activation of leptin signaling induced growth and motility in GBM cells. Interestingly, flow cytometry and real-time RT-PCR assays revealed that GBM cells, grown as neurospheres, displayed stem cell-like properties (CD133+) along with an enhanced expression of leptin receptors. Leptin treatment significantly increased the neurosphere forming efficiency, self-renewal capacity, and mRNA expression levels of the stemness markers CD133, Nestin, SOX2, and GFAP. Mechanistically, we evidenced a leptin-mediated upregulation of Notch 1 receptor and the activation of its downstream effectors and target molecules. Leptin-induced effects on U-87 MG and T98G cells were abrogated by the selective leptin antagonist, the peptide LDFI (Leu-Asp-Phe-Ile), as well as by the specific Notch signaling inhibitor, GSI (Gamma Secretase Inhibitor) and in the presence of a dominant-negative of mastermind-like-1. Overall, these findings demonstrate, for the first time, a functional interaction between leptin and Notch signaling in GBM, highlighting leptin/Notch crosstalk as a potential novel therapeutic target for GBM treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Leptin and Notch Signaling Cooperate in Sustaining Glioblastoma Multiforme Progression

et al. 2020

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“…FOS forms a tight complex (non-covalently) with the transcription factor JUN/AP-1, which plays important roles in the development of BC. 24,25 A recent study also found XHP could regulate the MEKK1/SEK1/JNK1/AP-1 pathway, which confirmed the possible interaction between XHP and the FOS/JUN/AP-1 complex. 26 Chen et al discovered that the overexpression of MMP9 stimulated the invasiveness of BC cell-formed spheroids in vitro and DCIS in vivo, whereas depletion of MMP9 inhibited their invasiveness.…”

Section: Discussionmentioning

confidence: 75%

<p>Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer</p>

Wu¹,

Luo²,

Li³

2020

BCTT

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“…Reporter luciferase activity was measured as described previously (27). In some experiments, pMMP1-Luc (−152/+87) and pMMP1-Luc (−152/+87)mtEGR-1 constructs were co-transfected with mammalian expression vectors for EGR-1 (pcDNA3.1/ EGR-1) or c-Jun (pcDNA3.1/Jun).…”

Section: Luciferase Promoter-reporter Assaymentioning

confidence: 99%

“…Isolation of total RNA and synthesis of complementary DNA (cDNA) were described elsewhere (27). The resulting cDNA was subjected to PCR analysis using gene-specific primers as follows: forward MMP-1, 5'-CAA AAT CCT GTC CAG CCC ATC G-3' and reverse MMP-1, 5'-TTC GTA AGC AGC TTC AAG CCC-3'; forward GAPDH, 5'-ACC CAC TCC TCC ACC TTT G-3' and reverse GAPDH, 5'-CTC TTG TGC TGC TGG G-3'.…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes

et al. 2020

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Matrix metalloproteinase 1 (MMP-1), a calcium-dependent zinccontaining collagenase, is involved in the initial degradation of native fibrillar collagen. Tissue necrosis factor-alpha (TNF) is a pro-inflammatory cytokine that is rapidly produced by dermal fibroblasts, monocytes/macrophages, and keratinocytes and regulates inflammation and damaged-tissue remodeling. MMP-1 is induced by TNF and plays a critical role in tissue remodeling and skin aging processes. However, the regulation of the MMP1 gene by TNF is not fully understood. We aimed to find additional cis-acting elements involved in the regulation of TNF-induced MMP1 gene transcription in addition to the nuclear factor-kappa B (NF-B) and activator protein 1 (AP1) sites. Assessments of the 5'-regulatory region of the MMP1 gene, using a series of deletion constructs, revealed the requirement of the early growth response protein 1 (EGR-1)-binding sequence (EBS) in the proximal region for proper transcription by TNF. Ectopic expression of EGR-1, a zinc-finger transcription factor that binds to G-C rich sequences, stimulated MMP1 promoter activity. The silencing of EGR-1 by RNA interference reduced TNF-induced MMP-1 expression. EGR-1 directly binds to the proximal region and transactivates the MMP1 gene promoter. Mutation of the EBS within the MMP1 promoter abolished EGR-1-mediated MMP-1 promoter activation. These data suggest that EGR-1 is required for TNF-induced MMP1 transcriptional activation. In addition, we found that all three MAPKs, ERK1/2, JNK, and p38 kinase, mediate TNF-induced MMP-1 expression via EGR-1 upregulation. These results suggest that EGR-1 may represent a good target for the development of pharmaceutical agents to reduce inflammation-induced MMP-1 expression. [

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Leptin stimulates IGF-1 transcription by activating AP-1 in human breast cancer cells

Cited by 22 publications

References 35 publications

Leptin and Notch Signaling Cooperate in Sustaining Glioblastoma Multiforme Progression

Leptin and Notch Signaling Cooperate in Sustaining Glioblastoma Multiforme Progression

<p>Network Pharmacology-Oriented Identification of Key Proteins and Signaling Pathways Targeted by Xihuang Pill in the Treatment of Breast Cancer</p>

Transcription factor EGR-1 transactivates the MMP1 gene promoter in response to TNFα in HaCaT keratinocytes

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