Receptor-interacting protein kinase 2 (RIPK2) stabilizes c-Myc and is a therapeutic target in prostate cancer metastasis

Yan, Yongnian; Zhou, Bo; Chen, Qian; Vasquez, Alex; Kamra, Mohini; Chatterjee, A.; Lee, Yeon‐Joo; Yuan, Xiaopu; Ellis, Leigh; Vizio, Dolores Di; Posadas, Edwin M.; Kyprianou, Natasha; Knudsen, Beatrice S.; Shah, Kavita; Murali, Ramachandran; Gertych, Arkadiusz; You, Sungyong; Freeman, Michael R.; Yang, Wei

doi:10.1038/s41467-022-28340-6

Cited by 26 publications

(14 citation statements)

References 79 publications

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“…Inhibition of RIPK2 can prevent the production of tumorigenic IL-17 in colorectal cancer (Garo et al 2021 ). Recent study showed that RIPK2 reduced prostate cancer metastasis through regulating c-Myc stability and activity (Yan et al 2022 ). Our study supplemented understanding on the role of RIPK2 in PC, indicating that the expression of RIPK2 was aberrantly increased in PC and a higher expression of RIPK2 predicted a poorer prognosis of PC patients.…”

Section: Discussionmentioning

confidence: 99%

Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation

Jiao

Ruan

Cheng

et al. 2023

Mol Med

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Background Protein kinases play a pivotal role in the malignant evolution of pancreatic cancer (PC) through mediating phosphorylation. Many kinase inhibitors have been developed and translated into clinical use, while the complex pathology of PC confounds their clinical efficacy and warrants the discovery of more effective therapeutic targets. Methods Here, we used the Gene Expression Omnibus (GEO) database and protein kinase datasets to map the PC-related protein kinase-encoding genes. Then, applying Gene Expression and Profiling Interactive Analysis (GEPIA), GEO and Human Protein Atlas, we evaluated gene correlation, gene expression at protein and mRNA levels, as well as survival significance. In addition, we performed protein kinase RIPK2 knockout and overexpression to observe effects of its expression on PC cell proliferation, migration and invasion in vitro, as well as cell apoptosis, reactive oxygen species (ROS) production and autophagy. We established PC subcutaneous xenograft and liver metastasis models to investigate the effects of RIPK2 knockout on PC growth and metastasis. Co-immunoprecipitation and immunofluorescence were utilized to explore the interaction between protein kinases RIPK2 and PRKCI. Polymerase chain reaction and immunoblotting were used to evaluate gene expression and protein phosphorylation level. Results We found fourteen kinases aberrantly expressed in human PC and nine kinases with prognosis significance. Among them, RIPK2 with both serine/threonine and tyrosine activities were validated to promote PC cells proliferation, migration and invasion. RIPK2 knockout could inhibit subcutaneous tumor growth and liver metastasis of PC. In addition, RIPK2 knockout suppressed autophagosome formation, increased ROS production and PC cell apoptosis. Importantly, another oncogenic kinase PRKCI could interact with RIPK2 to enhance the phosphorylation of downstream NF-κB, JNK and ERK. Conclusion Paired protein kinases PRKCI-RIPK2 with multiple phosphorylation activities represent a new pathological mechanism in PC and could provide potential targets for PC therapy.

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Section: Discussionmentioning

confidence: 99%

Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation

Jiao

Ruan

Cheng

et al. 2023

Mol Med

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“…As illustrated by these three models, there is a large overlap in the Myc, AR, PI3K, and Erk 1/2 signaling pathways—all of which are major oncogenic conduits leading to cell growth and proliferation. Furthermore, in the recent RIPK2 model, receptor-interacting protein kinase 2 (RIPK2) has been found to strongly regulate the stability and activity of c-Myc [ 109 ]. This is done through the association of RIPK2 with a form of MEK (MAPKK) called MAPKK7 [ 109 ].…”

Section: Mouse Models Based On Signaling Pathwaysmentioning

confidence: 99%

“…Furthermore, in the recent RIPK2 model, receptor-interacting protein kinase 2 (RIPK2) has been found to strongly regulate the stability and activity of c-Myc [ 109 ]. This is done through the association of RIPK2 with a form of MEK (MAPKK) called MAPKK7 [ 109 ]. Invasive adenocarcinoma with metastasis to bone is observed in this model.…”

Section: Mouse Models Based On Signaling Pathwaysmentioning

confidence: 99%

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In Vivo Models for Prostate Cancer Research

Adamiecki

Hryniewicz-Jankowska

Ortiz

et al. 2022

Cancers

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In 2022, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer in men in the United States—almost 270,000 American men are estimated to be diagnosed with PCa in 2022. This review compares and contrasts in vivo models of PCa with regards to the altered genes, signaling pathways, and stages of tumor progression associated with each model. The main type of model included in this review are genetically engineered mouse models, which include conditional and constitutive knockout model. 2D cell lines, 3D organoids and spheroids, xenografts and allografts, and patient derived models are also included. The major applications, advantages and disadvantages, and ease of use and cost are unique to each type of model, but they all make it easier to translate the tumor progression that is seen in the mouse prostate to the human prostate. Although both human and mouse prostates are androgen-dependent, the fact that the native, genetically unaltered prostate in mice cannot give rise to carcinoma is an especially critical component of PCa models. Thanks to the similarities between the mouse and human genome, our knowledge of PCa has been expanded, and will continue to do so, through models of PCa.

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“…The MYCN model and Braf V600E model are also accompanied by loss of Pten function. Furthermore, in the RIPK2 model, receptor-interacting protein kinase 2 (RIPK2) has been found to stabilize c-Myc, and is proposed as a therapeutic target in PCa metastasis [97]. As illustrated by these three models, there is a large overlap in the Myc, AR, and PI3K signaling pathways -all of which are major oncogenic conduits leading to cell growth and proliferation.…”

Section: Myc Pathwaymentioning

confidence: 99%

<em>In Vivo </em>Models for Prostate Cancer Research

Adamiecki¹,

Hryniewicz-Jankowska²,

Ortiz³

et al. 2022

Preprint

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In 2022, prostate cancer (PCa) is estimated to be the most commonly diagnosed cancer in men in the United States – almost 270,000 American men are estimated to be diagnosed with PCa in 2022 [1]. This review compares and contrasts in vivo models of PCa with regards to the altered genes, signaling pathways, and stages of tumor progression associated with each model. The main type of model included in this review are genetically engineered mouse models, which include conditional and constitutive knockout model. 2D cell lines, 3D organoids and spheroids, xenografts and allografts, and patient derived models are also included. The major applications, advantages and disadvantages, and ease of use and cost are unique to each type of model, but they all make it easier to translate the tumor progression that is seen in the mouse prostate to the human prostate. Although both human and mouse prostates are androgen-dependent, the fact that the native, genetically unaltered prostate in mice cannot give rise to carcinoma is an especially critical component of PCa models. Thanks to the similarities between the mouse and human genome, our knowledge of PCa has been expanded, and will continue to do so, through models of PCa.

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Receptor-interacting protein kinase 2 (RIPK2) stabilizes c-Myc and is a therapeutic target in prostate cancer metastasis

Cited by 26 publications

References 79 publications

Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation

Paired protein kinases PRKCI-RIPK2 promote pancreatic cancer growth and metastasis via enhancing NF-κB/JNK/ERK phosphorylation

In Vivo Models for Prostate Cancer Research

<em>In Vivo </em>Models for Prostate Cancer Research

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