PLCε knockdown inhibits prostate cancer cell proliferation via suppression of Notch signalling and nuclear translocation of the androgen receptor

Wang, Yin; Wu, Xiaohou; Ou, Liping; Yang, Xue; Wang, Xiaorong; Tang, Min; Chen, E.; Luo, Chunli

doi:10.1016/j.canlet.2015.03.018

Cited by 25 publications

(34 citation statements)

References 27 publications

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“…Two genome-wide studies identified single nucleotide polymorphisms in the PLCε gene in esophageal squamous cell carcinoma, providing additional evidence that PLCε acts as an oncogene leading to cell transformation (9,37). Our previous study demonstrated that PLCε expression was significantly higher in PCa tissues compared with normal prostate tissue, and PLCε knockdown resulted in reduced proliferation of PCa through downregulation of AR expression (10), and this result was confirmed in the present study. Additionally, the results of the present study revealed that PLCε regulation of AR may underlie the development of RT resistance in PCa.…”

Section: Discussionsupporting

confidence: 88%

“…This finding has been further verified by two genome-wide studies demonstrating that the PLCε gene is an essential tumor promoter in esophageal squamous cell carcinoma (9). Our previous study demonstrated that PLCε expression was significantly upregulated in PCa tissue compared with normal prostate tissue and that PLCε was capable of enhancing the proliferative ability and metastatic potential of PCa cells via various pathways (10)(11)(12). However, the association between PLCε and RT resistance in PCa has not been determined.…”

Section: Introductionmentioning

confidence: 70%

“…The thermocycling conditions were as follows: 95˚C for 30 sec, followed by 41 cycles of 95˚C for 10 sec, 60˚C for 30 sec and 72˚C for 30 sec. The mRNA expression levels were calculated using the comparative 2 -ΔΔCq method (10) and GAPDH served as the reference. All gene expression experiments were repeated at least three times.…”

Section: Immunohistochemistry (Ihcmentioning

confidence: 99%

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PLCε knockdown enhances the radiosensitivity of castration‑resistant prostate cancer via the AR/PARP1/DNA‑PKcs axis

Liu

et al. 2020

Oncol Rep

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Radiotherapy (RT) has been used as a therapeutic option for treatment of prostate cancer (PCa) for a number of years; however, patients frequently develop RT resistance, particularly in castration-resistant PCa (CRPC), although the underlying mechanisms remain unknown. Understanding the underlying mechanism of RT resistance in CRPC may potentially highlight novel targets to improve therapeutic options for patients with PCa. In the present study, the expression levels of phospholipase Cε (PLCε), androgen receptor (AR) and DNA-dependent protein kinase catalytic subunit (PKcs) were examined in PCa tissue samples and PCa cells, and the effects of PLCε knockdown on AR and DNA damage repair (DDR)-related molecules were determined. The association between PLCε, AR and Poly (ADP-ribose) polymerase 1 (PARP1), as well as their respective roles in radiation resistance, were assessed using gene knockdown and pharmaceutical inhibitors or activators. A chromatin immunoprecipitation assay was used to determine the epigenetic regulatory effects of PLCε on PARP1. Animal experiments were performed to assess whether the mechanisms observed in vitro could be replicated in vivo. The expression levels of PLCε, AR and DNA-PKcs were significantly upregulated in PCa, particularly in CRPC. PLCε knockdown reduced the viability and increased apoptosis of cells subjected to radiation. Additionally, PLCε deficiency suppressed DDR progression by downregulating an AR and PARP1 positive feedback loop and the associated downstream molecules following radiation. PLCε depletion also increased the presence of histone H3 lysine 27 trimethylation in the PARP1 promoter region, suggesting increased methylation of the PARP1 gene and thus resulting in reduced expression of PARP1. In vivo, PLCε knockdown significantly potentiated the effects of radiation on tumor growth. Taken together, the results of the present study demonstrated that PLCε knockdown enhanced the radiosensitivity of CRPC by downregulating the AR/PARP1/DNA-PKcs axis.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 70%

Section: Immunohistochemistry (Ihcmentioning

confidence: 99%

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PLCε knockdown enhances the radiosensitivity of castration‑resistant prostate cancer via the AR/PARP1/DNA‑PKcs axis

Liu

et al. 2020

Oncol Rep

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“…Both groups agree that inflammation mechanisms can be important triggers of skin cancer. The idea of inflammation as an intermediate mechanism that can lead to further tumor development has been given by authors who studied PLCε involvement in intestine cancer 24 and prostate cancer 60. The other studies support this idea, showing that PLCε is significantly involved in neuroinflammation (through the activation of NF-kB signaling) 70 and inflammatory response of epithelial cells during bronchial asthma (through the upregulation of inflammatory cytokines) 71.…”

Section: Plcε: a Critical But Controversial Player In Carcinogenesismentioning

confidence: 96%

“…The role of PLCε in prostate cancer has not been studied till recently, when the first article on this topic by Wang et al has been published 60. Authors investigated the expression of PLCε in 37 prostate cancer samples derived from cancer patients compared to 10 benign prostatic hyperplasia (BPH) specimens and also studied the relations among PLCε, androgen receptor AR and Notch1.…”

Section: Prostate Cancermentioning

confidence: 99%

The controversial role of phospholipase C epsilon (PLCε) in cancer development and progression

Tyutyunnykova¹,

Телегеев²,

Dubrovska³

2017

J. Cancer

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The phospholipase C (PLC) enzymes are important regulators of membrane phospholipid metabolism. PLC proteins can be activated by the receptor tyrosine kinases (RTK) or G-protein coupled receptors (GPCR) in response to the different extracellular stimuli including hormones and growth factors. Activated PLC enzymes hydrolyze phosphoinositides to increase the intracellular level of Ca2+ and produce diacylglycerol, which are important mediators of the intracellular signaling transduction. PLC family includes 13 isozymes belonging to 6 subfamilies according to their domain structures and functions. Although importance of PLC enzymes for key cellular functions is well established, the PLC proteins belonging to the ε, ζ and η subfamilies were identified and characterized only during the last decade. As a largest known PLC protein, PLCε is involved in a variety of signaling pathways and controls different cellular properties. Nevertheless, its role in carcinogenesis remains elusive.The aim of this review is to provide a comprehensive and up-to-date overview of the experimental and clinical data about the role of PLCε in the development and progression of the different types of human and experimental tumors.

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Signaling, Physiology, and Targeting of GPCR ‐Regulated Phospholipase C Enzymes

Chandan¹,

Smrcka²,

Phan³

2022

GPCRs as Therapeutic Targets

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PLCε knockdown inhibits prostate cancer cell proliferation via suppression of Notch signalling and nuclear translocation of the androgen receptor

Cited by 25 publications

References 27 publications

PLCε knockdown enhances the radiosensitivity of castration‑resistant prostate cancer via the AR/PARP1/DNA‑PKcs axis

PLCε knockdown enhances the radiosensitivity of castration‑resistant prostate cancer via the AR/PARP1/DNA‑PKcs axis

The controversial role of phospholipase C epsilon (PLCε) in cancer development and progression

Signaling, Physiology, and Targeting of GPCR ‐Regulated Phospholipase C Enzymes

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