Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK–Mediated Phosphorylation of Akt

Wang, Naitao; Yao, Ming; Xu, Jin; Quan, Yizhou; Zhang, Kaiqing; Yang, Ru; Gao, Wei‐Qiang

doi:10.1158/1078-0432.ccr-14-3163

Cited by 53 publications

(41 citation statements)

References 26 publications

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“…High M3 expression indicates a poor prognosis and shorter survival time in PDAC patients compared with patients with a low expression, which also related to lymph node involvement and AJCC stage. These results are in accordance with previous reports, which suggested that M3 is involved in the progression or prognosis in other cancers 5,9,10. Perineural invasion may include invasion to sympathetic nerve fiber, parasympathetic nerve fiber and sensory nerve fiber, and there is no detailed description on this aspect till now.…”

Section: Discussionsupporting

confidence: 94%

High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma

Zhang¹,

Xiu²,

Zhan

et al. 2016

OTT

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AimsRecent studies showed that muscarinic acetylcholine receptor 3 (M3), as a muscarinic acetylcholine receptor family member that plays an important role in normal physiological function, is engaged in cancer progression. However, the role of M3 in pancreatic ductal adenocarcinoma (PDAC) is not known. The aim of this study is to investigate the expression and prognostic value of M3 in patients with PDAC.Materials and methodsThe localization and expression of M3 in PDAC were examined by immunohistochemistry. VAChT was employed to detect parasympathetic nerve fibers in the corresponding M3 PDAC tissues. The correlation between M3 expression and patients’ survival was assessed by Kaplan–Meier analysis.ResultsM3 was discovered predominantly localized in the cell cytoplasm and expressed in all specimens of PDAC patients. Significant correlation was noted between increased M3 intensity and high grade of PDAC (P<0.01), more lymph node metastasis (P<0.01) as well as shorter patient overall survival (P<0.01). Morphologically, cells with high M3 expression were more frequently located at the invasive tumor front/tumor budding cells, metastatic lymph nodes and parasympathetic nerve fibers.ConclusionHigh expression of M3 is a prognostic marker for PDAC.

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Section: Discussionsupporting

confidence: 94%

High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma

Zhang¹,

Xiu²,

Zhan

et al. 2016

OTT

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“…Another interesting example of oncocrine signaling is the autocrine activation of muscarinic receptors in prostate cancer. In prostate cancer tissues, there is simultaneously an increased expression of choline acetyltransferase, the enzyme catalyzing the synthesis and secretion of acetylcholine, and M3 muscarinic receptors (CHRM3) (221). Experimentally, activation of acetylcholine receptors increases prostate cancer proliferation and migration (222).…”

Section: New "Oncocrine" Gpcrs Networkmentioning

confidence: 99%

Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy

Wu¹,

Yeerna²,

Nohata³

et al. 2019

Journal of Biological Chemistry

150

140

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Edited by Henrik G. Dohlman G protein-coupled receptors (GPCRs) are the largest gene family of cell membrane-associated molecules mediating signal transmission, and their involvement in key physiological functions is well-established. The ability of GPCRs to regulate a vast array of fundamental biological processes, such as cardiovascular functions, immune responses, hormone and enzyme release from endocrine and exocrine glands, neurotransmission, and sensory perception (e.g. vision, odor, and taste), is largely due to the diversity of these receptors and the layers of their downstream signaling circuits. Dysregulated expression and aberrant functions of GPCRs have been linked to some of the most prevalent human diseases, which renders GPCRs one of the top targets for pharmaceutical drug development. However, the study of the role of GPCRs in tumor biology has only just begun to make headway. Recent studies have shown that GPCRs can contribute to the many facets of tumorigenesis, including proliferation, survival, angiogenesis, invasion, metastasis, therapy resistance, and immune evasion. Indeed, GPCRs are widely dysregulated in cancer and yet are underexploited in oncology. We present here a comprehensive analysis of GPCR gene expression, copy number variation, and mutational signatures in 33 cancer types. We also highlight the emerging role of GPCRs as part of oncocrine networks promoting tumor growth, dissemination, and immune evasion, and we stress the potential benefits of targeting GPCRs and their signaling circuits in the new era of precision medicine and cancer immunotherapies. The G protein-coupled receptor (GPCR) 7 family of proteins includes over 800 members and comprises ϳ4% of the encoded human genome, making it the largest gene family involved in signal transduction (1, 2). Common to all GPCRs is the 7-transmembrane domain structure, which has an extracellular N terminus and an intracellular C terminus. The importance of the multiple biological roles GPCRs is reflected in the range of key physiological processes that they regulate, including vision, olfaction, neurotransmission, hormone and enzyme release, immune response, hemostasis, cardiac response and blood pressure regulation, epithelial cell renewal, stem cell fate decisions, tissue development, and homeostasis. In fact, dysfunction of GPCRs contributes to some of the most prevalent

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“…The present study aimed to identify pathways mediating proliferation and metastasis in HCC. The PI3K/AKT pathway, which regulates growth and invasion during cancer development, including HCC, was studied (20,21). Following suppression of RASAL2, the phosphorylation levels of AKT were reduced in the two HCC cell lines.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of RASAL2 promotes proliferation and metastasis, and is targeted by miR-203 in hepatocellular carcinoma

Fang

Zhao

Wang

et al. 2017

Molecular Medicine Reports

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RAS protein activator like 2 (RASAL2) has been reported to be dysregulated in various types of cancer. It has previously been demonstrated that RASAL2 is hypomethylated in hepatocellular carcinoma (HCC). However, the expression pattern of RASAL2 and its potential role in HCC remain to be elucidated. The present study demonstrated that the expression of RASAL2 was upregulated in HCC tissues, compared with in normal liver tissues, by using immunohistochemistry. In addition, Cell Counting Kit-8 assay and invasion assay revealed that knockdown of RASAL2 inhibited the growth and invasion of HCC cells. Western blotting results indicated that the inhibition of RASAL2 reduced the levels of phosphorylated-AKT. Notably, RASAL2 was observed to be a direct target of miR-203 in HCC in luciferase activity assays. Furthermore, overexpression of miR-203 exhibited a similar effect to RASAL2 knockdown in HCC cells. These results indicated that RASAL2 serves a tumor oncogenic role in HCC and may be considered a potential target in HCC.

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Autocrine Activation of CHRM3 Promotes Prostate Cancer Growth and Castration Resistance via CaM/CaMKK–Mediated Phosphorylation of Akt

Cited by 53 publications

References 26 publications

High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma

High expression of muscarinic acetylcholine receptor 3 predicts poor prognosis in patients with pancreatic ductal adenocarcinoma

Illuminating the Onco-GPCRome: Novel G protein–coupled receptor-driven oncocrine networks and targets for cancer immunotherapy

Upregulation of RASAL2 promotes proliferation and metastasis, and is targeted by miR-203 in hepatocellular carcinoma

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