PLCε signaling in cancer

Zhang, Ruiyan; Du, Wen‐Qi; Zhang, Yingchun; Zheng, Junnian; Pei, Dong‐Sheng

doi:10.1007/s00432-015-1999-x

Cited by 13 publications

(12 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, it is worth exploring whether PKCε activation is related to prostate cancer progression. In previous studies from our research group and others, PLCε has been suggested to play an important role in human malignancies (32)(33)(34)(35)(36). In addition, PLCε as a subtype of the PLC family has a unique structure: RA domain may directly bind to the RAS gene family and the common structures of the PLC family: EF, X, and F can activate DAG/CA2+ to activate PKC (37).…”

Section: Introductionmentioning

confidence: 77%

RETRACTED: Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway

et al. 2020

View full text Add to dashboard Cite

Castration-resistant prostate cancer (CRPC) is a progressed stage of prostate cancer, which requires better understanding of the mechanisms and remains an unmet clinical need. As a common oncogene, K-Ras is associated with malignant behavior in different types of tumors but its role in CRPC is unknown. The present study aims to find the mechanism of K-Ras in CRPC and whether it can be used as a crucial molecule for the treatment of CRPC. For this purpose, tissue samples from primary prostate cancer (PPC) and CRPC patients were analyzed by immunohistochemistry and the data showed that K-Ras was elevated in CRPC. More importantly, higher K-Ras expression was related to a shorter recurrence-free survival time in patients with CRPC. In addition, K-Ras promoted the invasion, migration, and drug resistance of CRPC cells by activation of PLCε/PKCε signaling pathway. Meanwhile, the inhibitor of K-RasG12C mutants was able to inhibit malignant behavior of CRPC cells in vitro and in vivo. Inhibitors of K-RasG12C mutants have entered clinical trials. Taken together, the study shows that K-Ras may activate PKCε through PLCε, resulting in the alterations of malignant behavior of CRPC. Inhibitor 9, an inhibitor of the K-RasG12C mutant, has a strong anti-tumor effect in CRPC, which potentially suggests that inhibitors of this nature may serve as a promising treatment for CRPC.

show abstract

Section: Introductionmentioning

confidence: 77%

RETRACTED: Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway

et al. 2020

View full text Add to dashboard Cite

show abstract

“…PLCE1 is a multifunctional signaling protein that may act as an oncoprotein, promoting malignant transformation of primary cell lines, tumor growth, migration, and metastasis in various human cancers [7, 8]. Previous work confirmed a greater expression of PLCE1 protein in homozygous mutant types of rs12263737 and rs2274223 carriers than in homozygous wild-type control carriers [6, 26].…”

Section: Discussionmentioning

confidence: 99%

“…Phospholipase C epsilon 1 (PLCE1) was identified as a member of the phospholipase family, which is essential for intracellular signaling by catalyzing hydrolysis of a membrane phospholipid, i.e., phosphatidylinositol-4,5-bisphosphate, to generate two important secondary messengers, i.e., diacylglycerol and inositol 1,4,5-trisphosphate [4–6]. PLCE1 was identified to mediate diverse external signals and has been reported to correlate with tumor clinical stages and survival, including hepatocellular carcinoma, colorectal, bladder, gastric, head and neck, and gallbladder cancers [2, 7, 8]. Recent genome-wide association studies (GWAS) indicated that single-nucleotide polymorphisms (SNPs) in PLCE1 can affect gene expression, protein functions, and risk for ESCC [4].…”

Section: Introductionmentioning

confidence: 99%

Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/ Bcl-2 expression

et al. 2019

View full text Add to dashboard Cite

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies. Neovascularization during tumorigenesis supplies oxygen and nutrients to proliferative tumor cells, and serves as a conduit for migration. Targeting oncogenes involved in angiogenesis is needed to treat organ-confined and locally advanced ESCC. Although the phospholipase C epsilon-1 (PLCE1) gene was originally identified as a susceptibility gene for ESCC, how PLCE1 is involved in ESCC is unclear.MethodsMatrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to measure the methylation status of the PLCE1 promoter region. To validate the underlying mechanism for PLCE1 in constitutive activation of the NF-κB signaling pathway, we performed studies using in vitro and in vivo assays and samples from 368 formalin-fixed esophageal cancer tissues and 215 normal tissues with IHC using tissue microarrays and the Cancer Genome Atlas dataset.ResultsWe report that hypomethylation-associated up-regulation of PLCE1 expression was correlated with tumor angiogenesis and poor prognosis in ESCC cohorts. PLCE1 can activate NF-κB through phosphoinositide-phospholipase C-ε (PI-PLCε) signaling pathway. Furthermore, PLCE1 can bind p65 and IκBα proteins, promoting IκBα-S32 and p65-S536 phosphorylation. Consequently, phosphorylated IκBα promotes nuclear translocation of p50/p65 and p65, as a transcription factor, can bind vascular endothelial growth factor-C and bcl-2 promoters, enhancing angiogenesis and inhibiting apoptosis in vitro. Moreover, xenograft tumors in nude mice proved that PLCE1 can induce angiogenesis, inhibit apoptosis, and increase tumor aggressiveness via the NF-κB signaling pathway in vivo.ConclusionsOur findings not only provide evidence that hypomethylation-induced PLCE1 confers angiogenesis and proliferation in ESCC by activating PI-PLCε-NF-κB signaling pathway and VEGF-C/Bcl-2 expression, but also suggest that modulation of PLCE1 by epigenetic modification or a selective inhibitor may be a promising therapeutic approach for the treatment of ESCC.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0930-x) contains supplementary material, which is available to authorized users.

show abstract

“…Therefore, BBN-induced bladder cancer is similar to transitional cell carcinoma in patients in both kinetic and histological features ( 28 ). PLCε is important in the development and progression of human cancer types ( 29 ). The present study used BBN to induce bladder cancer, and knockout of PLCε attenuated BBN-induced tumorigenesis of bladder cancer.…”

Section: Discussionmentioning

confidence: 99%

Knockout of phospholipase Cε attenuates N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumorigenesis

TaiMao

Liu

et al. 2016

Molecular Medicine Reports

View full text Add to dashboard Cite

Bladder cancer frequently shows mutational activation of the oncogene Ras, which is associated with bladder carcinogenesis. However, the signaling pathway downstream of Ras remains to be fully elucidated. N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) is able to induce bladder cancer by driving the clonal expansion of initiated cells carrying the activated form of Ras. Phospholipase Cε (PLCε) is the main target of BBN, while the tumor promoting role of PLCε remains controversial. The present study examined the role of PLCε in BBN-induced bladder carcinogenesis of mice with genetically inactivated PLCε. Using light and electron microscopy, the present study demonstrated that PLCε−/− mice were resistant to BBN-induced bladder carcinogenesis. Furthermore, it was demonstrated that cyclooxygenase 2 and vascular endothelial growth factor-A were affected by the PLCε background of the mice, suggesting that the role of PLCε in tumor promotion may be ascribed to augmentation of inflammatory responses and angiogenesis. These results indicated that PLCε is crucial for BBN-induced bladder carcinogenesis as well as signaling downstream of Ras, and that PLCε is a candidate molecular target for the development of anti-cancer drugs.

show abstract

PLCε signaling in cancer

Cited by 13 publications

References 78 publications

RETRACTED: Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway

RETRACTED: Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway

Epigenetically upregulated oncoprotein PLCE1 drives esophageal carcinoma angiogenesis and proliferation via activating the PI-PLCε-NF-κB signaling pathway and VEGF-C/ Bcl-2 expression

Knockout of phospholipase Cε attenuates N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder tumorigenesis

Contact Info

Product

Resources

About