Prostate cancer, PI3K, PTEN and prognosis

Wise, Helen; Hermida, Miguel A.; Leslie, Nicholas

doi:10.1042/cs20160026

Cited by 158 publications

(128 citation statements)

References 152 publications

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“…PTEN resulted in dysregulated activation of the PI3K signaling network, which is recognized as one of the most common driving events in prostate cancer development [47]. Recently, as a new agent, PTEN has been recommended to fight against fibrogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of PTEN function, one of the most common driving events in cancer development [7], resulted in dysregulated activation of the phosphoinositide 3-kinase (PI3K) signaling network. Recently, more scholars have discovered that PTEN plays an important role in mediating fibrosis development in vital organs such as the liver, lung and kidneys by activating profibrotic signaling pathways [8-10].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia Reperfusion-Induced Acute Kidney Injury

Zhou

Zhong

Shi

et al. 2017

Cell Physiol Biochem

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Background: Renal fibrosis is a common pathophysiological feature of chronic kidney disease. Acute kidney injury (AKI) is defined as an independent causal factor of chronic kidney disease, with a pathological representation of post renal fibrosis. However, the etiopathogenesis underlying post renal fibrosis induced by AKI is not completely understood. Methods: BALB/c mice were treated with bpv or vehicle controls and were, respectively, the ischemia reperfusion (IR) model group and control group. All of the animals had blood taken from the orbital venous plexus at 24 hours after IR. Six mice in each group were randomly chosen and euthanized 7 days after IR treatment, and the remaining six mice in each group were euthanized 14 days after IR treatment. We examined the effect on post kidney fibrosis of inhibiting PTEN activity in mice in an IR induced AKI experimental model. Results: Compared with vehicle mice, bpv-(PTEN specific inhibitor) treated mice accumulated more bone marrow-derived fibroblasts and myofibroblasts in the kidneys. Inhibition of PTEN activity increased the expression of α-smooth muscle actin and extracellular matrix proteins and post kidney fibrosis. Furthermore, inhibition of PTEN activity resulted in more inflammatory cytokines in the kidneys of mice subjected to IR-induced renal fibrosis. Moreover, inhibition of PTEN activity up-regulated PI3K protein expression and Akt phosphorylation. Conclusions: Our study demonstrated that PTEN played an important role in post renal fibrosis in mice with ischemia reperfusion-induced AKI. These results indicated that the PTEN/PI3K/Akt signaling pathway may serve as a novel therapeutic target for AKI-induced chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia Reperfusion-Induced Acute Kidney Injury

Zhou

Zhong

Shi

et al. 2017

Cell Physiol Biochem

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“…Growth factors bind to their receptors, receptor auto-phosphorylation occurs leading to activation of downstream signaling cascades such as the phosphoinositide-3-kinase (PI3K)/Protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway that results in increased survival/proliferation and inhibition of apoptosis [10,11,12,13]. Another pathway activated by GF signaling is the RAS/mitogen activated protein kinases (MAPK) pathway.…”

Section: Introductionmentioning

confidence: 99%

Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies

Yousef

Tsiani

2017

Cancers

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Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival and these mutations allow them to develop resistance to many chemotherapeutic agents, highlighting the need for development of new potent anti-cancer agents. Metformin has long been used as a treatment for type 2 diabetes and has recently attracted attention as a potential agent to be used in the treatment of cancer. The present review summarizes the existing in vitro and in vivo animal studies focusing on the anti-lung cancer effects of metformin and its effects on key proliferative and anti-apoptotic signaling pathways.

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“…PTEN (phosphatase and tensin homolog deleted on chromosome 10) is a dual-specificity phosphatase and critical tumor suppressor whose expression is downregulated and/or lost in many tumor types 24 . PTEN loss has correlated with activation of the PI3K-AKT pathway, which is implicated in the pathogenesis of these cancers, and is particularly relevant in prostate cancer [25][26][27][28] . Deleterious PTEN alterations are found in up to ~20-30% of primary prostate cancer tissues and in ~40-60% of metastatic tissues, and are among the most common genomic events in prostate cancer [29][30][31] .…”

Section: Introductionmentioning

confidence: 99%

Chemerin increases T-cell mediated cytotoxicity of human tumors via modulation of a novel CMKLR1/PTEN/PD-L1 axis

Rennier

Krug

Virdi

et al. 2019

Preprint

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Chemerin (RARRES2) is an endogenous leukocyte chemoattractant known to recruit innate immune cells through its chemotactic receptor, CMKLR1. RARRES2 is often downregulated in prostate cancer and across multiple tumor types compared to normal tissue. Additionally, a methylome-wide analysis identified RARRES2 as one of the most hypermethylated genes in sarcoma. Recent studies have shown that augmenting chemerin in the tumor microenvironment significantly suppresses tumor growth, at least in part by recruitment of immune effector cells. However, as tumor cells have been shown to express functional chemokine receptors that can impact their phenotype, we hypothesized that chemerin might have additional, tumor-intrinsic effects. Here, we show for the first time that human cancer cells exposed to exogenous chemerin significantly upregulate PTEN expression and activity. Additionally, chemerin-induced PTEN expression correlated with a concomitant reduction in PD-L1 mRNA and protein expression. Chemerin treatment of tumor cells led to significantly reduced tumor cell migration/invasion, as well as significantly increased cytotoxicity by T cells. siRNA knockdown of tumor expressed CMKLR1 abrogated chemerin-induced modulation of PTEN and PD-L1 expression and activity, supporting the presence of a CMKLR1/PTEN/PD-L1 signaling cascade. We then compared chemerin treatment to PD-L1 inhibition by siRNA knockdown or the antagonistic antibody atezolizumab in T cell cytotoxicity assays and surprisingly found chemerin treatment was as effective as both Chemerin modulates PTEN/PD-L1 via CMKLR1 in human tumors Page 2 of 29 PD-L1 knockdown and atezolizumab treatment in mediating tumor lysis. Collectively, our data show a novel link between chemerin, PTEN and PD-L1 in human tumor lines, with functional consequences that may have a role in improving T cell-mediated immunotherapies. Runnning Title: Chemerin modulates PTEN/PD-L1 via CMKLR1 in human tumors Word Counts: Abstract -250

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Prostate cancer, PI3K, PTEN and prognosis

Cited by 158 publications

References 152 publications

Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia Reperfusion-Induced Acute Kidney Injury

Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia Reperfusion-Induced Acute Kidney Injury

Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies

Chemerin increases T-cell mediated cytotoxicity of human tumors via modulation of a novel CMKLR1/PTEN/PD-L1 axis

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