The emerging roles of GPRC5A in diseases

Zhou, Honglei; Rigoutsos, Isidore

doi:10.18632/oncoscience.104

Cited by 65 publications

(71 citation statements)

References 90 publications

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“…GPRC5A is known to contain a binding site for CREB in the 5′ promotor region. Therefore, GPRC5A may form a negative feedback loop in which the phosphorylation of CREB is suppressed . The small molecule forskolin can promote CREB phosphorylation .…”

Section: Discussionmentioning

confidence: 99%

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GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer

Sawada

Kikugawa

Iio

et al. 2019

Intl Journal of Cancer

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The prognosis of patients with progressive prostate cancers that are hormone refractory and/or have bone metastasis is poor. Multiple therapeutic targets to improve prostate cancer patient survival have been investigated, including orphan GPCRs. In our study, we identified G Protein‐Coupled Receptor Class C Group 5 Member A (GPRC5A) as a candidate therapeutic molecule using integrative gene expression analyses of registered data sets for prostate cancer cell lines. Kaplan–Meier analysis of TCGA data sets revealed that patients who have high GPRC5A expression had significantly shorter overall survival. PC3 prostate cancer cells with CRISPR/Cas9‐mediated GPRC5A knockout exhibited significantly reduced cell proliferation both in vitro and in vivo. RNA‐seq revealed that GPRC5A KO PC3 cells had dysregulated expression of cell cycle‐related genes, leading to cell cycle arrest at the G2/M phase. Furthermore, the registered gene expression profile data set showed that the expression level of GPRC5A in original lesions of prostate cancer patients with bone metastasis was higher than that without bone metastasis. In fact, GPRC5A KO PC3 cells failed to establish bone metastasis in xenograft mice models. In addition, our clinical study revealed that GPRC5A expression levels in prostate cancer patient samples were significantly correlated with bone metastasis as well as the patient's Gleason score (GS). Combined assessment with the immunoreactivity of GPRC5A and GS displayed higher specificity for predicting the occurrence of bone metastasis. Together, our findings indicate that GPRC5A can be a possible therapeutic target and prognostic marker molecule for progressive prostate cancer.

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Section: Discussionmentioning

confidence: 99%

“…GPRC5A participates in lung tissue homeostasis, and is expressed in pulmonary epithelial cells . Several reports showed that GPRC5A expression is increased in pancreatic cancer, colon cancer, breast cancer and myelodysplastic syndrome . On the other hand, GPRC5A has a dual behavior as a tumor suppressor.…”

Section: Introductionmentioning

confidence: 99%

GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer

Sawada

Kikugawa

Iio

et al. 2019

Intl Journal of Cancer

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“…GPRC5a is over expressed in pancreatic, breast, gastric and colon cancer, and it has been shown that overexpression of RAI3 predict poor prognosis in hepatocellular carcinoma [5–11]. Functional analysis of GPRC5a in different carcinomas indicated that RAI3 has pleiotropic effects and might confer resistance to Gemcitabine in pancreatic cancer, however the ligand of GPRC5a remains elusive [12], but GPRC5a overexpression might lead to a reduction of EGFR levels [13–16]. …”

Section: Introductionmentioning

confidence: 99%

The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation

et al. 2017

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Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest tumors worldwide. Understanding the function of gene expression alterations is a prerequisite for developing new strategies in diagnostic and therapy. GPRC5A (RAI3), coding for a seven transmembrane G protein-coupled receptor is known to be overexpressed in pancreatic cancer and might be an interesting candidate for therapeutic intervention. Expression levels of RAI3 were compared using a tissue microarray of 435 resected patients with pancreatic cancer as well as 209 samples from chronic pancreatitis (CP), intra-ductal papillary mucinous neoplasm (IPMN) and normal pancreatic tissue. To elucidate the function of RAI3 overexpression, siRNA based knock-down was used and transfected cells were analyzed using proliferation and migration assays. Pancreatic cancer patients showed a statistically significant overexpression of RAI3 in comparison to normal and chronic pancreatitis tissue. Especially the loss of apical RAI3 expression represents an independent prognostic parameter for overall survival of patients with pancreatic cancer. Suppression of GPRC5a results in decreased cell growth, proliferation and migration in pancreatic cancer cell lines via a STAT3 modulated pathway, independent from ERK activation.

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“…GPRC5A also interacted with multiple proteins including EIF4A1 and HSPA9. Some studies even found GPRC5A was co-fractionated with GTF2F2, MPV17, NOLC1, SLC25A3, and EGFR in vivo [20,21]. GPRC5A was also involved in regulating the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

GPRC5A overexpression predicted advanced biological behaviors and poor prognosis in patients with gastric cancer

et al. 2015

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G protein-coupled receptor, family C, group 5, member A (GPRC5A) had received attentions for its role in carcinogenesis and prognostic values in several types of cancer. However, the functional roles of GPRC5A in gastric cancer (GC) had never been elucidated. The expression levels of GPRC5A were detected by real-time quantitative reverse transcription PCR and Western blot in GC tissues and adjacent non-tumor tissues. GPRC5A expression in tissue sections of 106 GC samples was evaluated using immunohistochemistry. The staining results were compared with clinicopathological factors and to the prognosis of GC patients. The mRNA and protein expression levels of GPRC5A in gastric cancer tissues were higher than those in adjacent non-tumor tissues. Positive GPRC5A expression was significantly correlated with larger size of primary tumor, diffuse type (Lauren's classification), deeper serosal invasion, and more lymph node metastasis. In addition, Kaplan-Meier curve analysis demonstrated that GC patients with positive GPRC5A expression had poor prognosis than those with negative GPRC5A expression. GPRC5A expression was identified as an independent factor of the overall survival in GC patients by multivariate Cox analysis. Further, the overall survival difference existed between patients with GPRC5A positive and negative groups in GC patients with lymph node metastasis. Our results suggested that elevated levels of GPRC5A played significant roles in GC progression. GPRC5A could serve as a prognostic biomarker of GC.

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The emerging roles of GPRC5A in diseases

Cited by 65 publications

References 90 publications

GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer

GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer

The G Protein-Coupled Receptor RAI3 Is an Independent Prognostic Factor for Pancreatic Cancer Survival and Regulates Proliferation via STAT3 Phosphorylation

GPRC5A overexpression predicted advanced biological behaviors and poor prognosis in patients with gastric cancer

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