Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway

Li, Jinping; Wang, Enfeng; Rinaldo, Francesca; Datta, Kaustubh

doi:10.1038/sj.onc.1208693

Cited by 58 publications

(70 citation statements)

References 61 publications

(56 reference statements)

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“…This finding suggests that RalA is activated within 72 h of androgen deprivation in human prostate carcinoma cells. Of note, our previous findings (Li et al, 2005) also support a significant upregulation of VEGF-C in LNCaP after 72 h under androgen-ablated conditions. We have also observed a detectable increase in ROS level at 72 h after androgen withdrawal ( Figure 1).…”

Section: Rala-ros Signaling Axis Regulates Vegf-c Synthesis F Rinaldosupporting

confidence: 60%

“…We have previously shown that in response to androgen deprivation, VEGF-C mRNA and protein levels are elevated (B3-to 7-fold) in a time-dependent manner (Li et al, 2005). Following our observation that androgen negatively regulates VEGF-C synthesis, publications describing androgen deprivation-induced upregulation of intracellular ROS in the rat prostate came to our attention (Tam et al, 2003).…”

Section: Androgen Deprivation Results In Increased Intracellular Ros mentioning

confidence: 90%

“…Despite this evidence for the role of VEGF-C in advanced stage prostate cancer, the molecular mechanism involved in VEGF-C expression is still poorly understood. In a previous publication, we show that androgen-ablated conditions and a decrease in insulin-like growth factor 1-receptor (IGF-1R) signaling leads to activation of the forkhead transcription factor FOXO-1 and a concomitant upregulation of VEGF-C mRNA synthesis (Li et al, 2005). However, the IGF-1R pathway for FOXO-1 activation is not the only pathway involved in the transcriptional regulation of VEGF-C under androgen-ablated conditions.…”

Section: Introductionmentioning

confidence: 99%

“…Other studies have shown a strong correlation between VEGF-C and its receptor VEGF-R3 (flt4) expression and lymph node metastasis in human prostate carcinoma tissue (Tsurusaki et al, 1999;Jennbacken et al, 2005;Zeng et al, 2005). Previously, we have shown that in the prostate cancer cell line LNCaP, VEGF-C upregulation can also lead to an increase in androgen receptor co-activator, Bag-1L, suggesting that VEGF-C has the ability to transactivate androgen receptor under low androgen concentrations (Li et al, 2005). Taken together, these findings suggest multiple functions for VEGF-C in prostate cancer progression.…”

Section: Introductionmentioning

confidence: 99%

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RalA regulates vascular endothelial growth factor-C (VEGF-C) synthesis in prostate cancer cells during androgen ablation

Rinaldo

Wang

et al. 2006

Oncogene

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Section: Rala-ros Signaling Axis Regulates Vegf-c Synthesis F Rinaldosupporting

confidence: 60%

Section: Androgen Deprivation Results In Increased Intracellular Ros mentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

RalA regulates vascular endothelial growth factor-C (VEGF-C) synthesis in prostate cancer cells during androgen ablation

Rinaldo

Wang

et al. 2006

Oncogene

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“…The relevance of Sp1 and Sp3 in estradiol regulation of VEGF in breast cancer was suggested by binding assays in vitro (by EMSA) and in vivo (by ChIP). Similarly, multiple groups have shown that androgen treatment of human fetal fibroblasts and LNCaP cells significantly increases VEGF mRNA expression levels (110)(111)(112)102). Additionally, VEGF protein levels have been demonstrated to be upregulated after the treatment of LNCaP cells with hormone (106), and the androgen antagonist flutamide blocked this upregulation (113).…”

Section: Combined Androgen and Wt1 Activation Of Vegf Expression In Hmentioning

confidence: 99%

Functional Role of WT1 in Prostate Cancer

et al. 2016

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Licence: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Users are allowed to share (copy and redistribute the material in any medium or format) and adapt (remix, transform, and build upon the material for any purpose, even commercially), as long as the authors and the publisher are explicitly identified and properly acknowledged as the original source. AbstractAlthough initial discoveries of Wilms tumor 1 (WT1) expression in extrarenal disease generated controversy, we and others have examined WT1 expression in non-Wilms cancers and have demonstrated that the WT1(A) isoform, lacking the lysine-threonine-serine tripeptide (KTS) insertion, transcriptionally regulates the expression of growth control genes in other cancer types. Here, we review our evidence that WT1 is expressed in prostate cancer (PC) epithelial cells and regulates PC critical genes. That WT1 may promote metastatic disease is consistent with previous findings that WT1 suppressed E-cadherin and enhanced motility of PC cells with low migratory and metastatic potential. Recent findings led us to askFraizer et al. 236whether WT1 acts as an angiogenic switch in PC. Although vascular endothelial growth factor (VEGF) is regulated at several levels and by a number of different factors, a mechanistic understanding of WT1-mediated transcriptional regulation in PC cells was previously lacking. Here, we discuss the evidence of WT1-and androgen receptor (AR)-binding sites in the VEGF promoter and show the potential for cooperation between hormone and WT1. These findings revealed that in AR-intact PC cells, WT1 was sufficient to upregulate VEGF transcription, and WT1 expression enhanced the hormone activation of VEGF expression. This notion that WT1 can activate an angiogenic switch in PC cells, to enhance tumor growth and progression to metastatic disease, is consistent with our understanding of the oncogenic nature of WT1 overexpression in inappropriate tissues or at inappropriate times. The potential for WT1 to promote both tumor angiogenesis and PC cell migration suggests that WT1 regulates genes that promote PC progression to lethal metastatic disease. Therapies targeting WT1 in PC may reduce metastatic spread and increase overall survival.

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Comprehensive pan‐cancer analysis of mitochondrial outer membrane permeabilisation activity reveals positive immunomodulation and assists in identifying potential therapeutic targets for immunotherapy resistance

Chen,

Gao,

et al. 2024

Clinical & Translational Med

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BackgroundMitochondrial outer membrane permeabilisation (MOMP) plays a pivotal role in cellular death and immune activation. A deeper understanding of the impact of tumour MOMP on immunity will aid in guiding more effective immunotherapeutic strategies.MethodsA comprehensive pan‐cancer dataset comprising 30 cancer‐type transcriptomic cohorts, 20 immunotherapy transcriptomic cohorts and three immunotherapy scRNA‐seq datasets was collected and analysed to determine the influence of tumour MOMP activity on clinical prognosis, immune infiltration and immunotherapy effectiveness. Leveraging 65 scRNA‐Seq datasets, the MOMP signature (MOMP.Sig) was developed to accurately reflect tumour MOMP activity. The clinical predictive value of MOMP.Sig was explored through machine learning models. Integration of the MOMP.Sig model and a pan‐cancer immunotherapy CRISPR screen further investigated potential targets to overcome immunotherapy resistance, which subsequently underwent clinical validation.ResultsOur research revealed that elevated MOMP activity reduces mortality risk in cancer patients, drives the formation of an anti‐tumour immune environment and enhances the response to immunotherapy. This finding emphasises the potential clinical application value of MOMP activity in immunotherapy. MOMP.Sig, offering a more precise indicator of tumour cell MOMP activity, demonstrated outstanding predictive efficacy in machine‐learning models. Moreover, with the assistance of the MOMP.Sig model, FOXO1 was identified as a core modulator that promotes immune resistance. Finally, these findings were successfully validated in clinical immunotherapy cohorts of skin cutaneous melanoma and triple‐negative breast cancer patients.ConclusionsThis study enhances our understanding of MOMP activity in immune modulation, providing valuable insights for more effective immunotherapeutic strategies across diverse tumours.

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Upregulation of VEGF-C by androgen depletion: the involvement of IGF-IR-FOXO pathway

Cited by 58 publications

References 61 publications

RalA regulates vascular endothelial growth factor-C (VEGF-C) synthesis in prostate cancer cells during androgen ablation

RalA regulates vascular endothelial growth factor-C (VEGF-C) synthesis in prostate cancer cells during androgen ablation

Functional Role of WT1 in Prostate Cancer

Comprehensive pan‐cancer analysis of mitochondrial outer membrane permeabilisation activity reveals positive immunomodulation and assists in identifying potential therapeutic targets for immunotherapy resistance

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