Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis
Background: Tumor angiogenesis is essential for colorectal cancer (CRC) progression, providing oxygen and nutrients to sustain tumor growth and metastasis. Protein kinase C iota (Prkci) is an atypical protein kinase known for its oncogenic roles in various cancers; however, its function in CRC angio...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000983 |
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| _version_ | 1849229327554576384 |
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| author | Peng Li Guangshi Liu Wenbin Zhang Tao Li Xinhui Yang |
| author_facet | Peng Li Guangshi Liu Wenbin Zhang Tao Li Xinhui Yang |
| author_sort | Peng Li |
| collection | DOAJ |
| description | Background: Tumor angiogenesis is essential for colorectal cancer (CRC) progression, providing oxygen and nutrients to sustain tumor growth and metastasis. Protein kinase C iota (Prkci) is an atypical protein kinase known for its oncogenic roles in various cancers; however, its function in CRC angiogenesis remains largely unexplored. This study investigates the role of Prkci in regulating tumor angiogenesis through the Jak2/Stat3 signaling pathway. Methods: Prkci expression levels in CRC tissues and their correlation with micro-vessel density and patient prognosis were analyzed. Functional experiments, including endothelial cell proliferation, migration, and tube formation assays, were performed in vitro to assess the angiogenic effects of Prkci. In vivo, a CRC xenograft mouse model with Prkci knockout was used to evaluate tumor growth and angiogenesis. Mechanistic studies explored how Prkci activates Jak2 by phosphorylating it at the S633 site, leading to downstream Stat3 activation and Vegfa expression. Results: Prkci was upregulated in CRC tissues and correlated with increased micro-vessel density and poor patient prognosis. In vitro, Prkci overexpression enhanced endothelial cell proliferation, migration, and tube formation, while Prkci knockout inhibited these processes. Mechanistically, Prkci phosphorylated Jak2 at S633, leading to enhanced Stat3 activation and increased Vegfa expression, which promoted angiogenesis. In vivo, Prkci knockout in CRC cells significantly reduced tumor growth, angiogenesis, and prolonged survival in a mouse model. Conclusions: These findings identify Prkci as a key regulator of angiogenesis in CRC through Jak2/Stat3 signaling activation. Targeting Prkci could provide a novel therapeutic approach to inhibit tumor angiogenesis and limit CRC progression. |
| format | Article |
| id | doaj-art-b35f27bba46548c3b6844d7c6b065d2a |
| institution | Kabale University |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-b35f27bba46548c3b6844d7c6b065d2a2025-08-22T04:55:52ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-10-016810121910.1016/j.neo.2025.101219Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesisPeng Li0Guangshi Liu1Wenbin Zhang2Tao Li3Xinhui Yang4Gastrointestinal Surgery department, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, Urumqi 830000, ChinaGastrointestinal Surgery department, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, Urumqi 830000, ChinaDepartment of Gastrointestinal Surgery, Xinjiang Medical University Affiliated Cancer Hospital, Gastrointestinal Surgery department, Xinjiang, Urumqi 830000, ChinaGastrointestinal Surgery department, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, Urumqi 830000, ChinaGastrointestinal Surgery department, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang, Urumqi 830000, China; Corresponding author at: People’s Hospital of Xinjiang Uygur Autonomous Region, Gastrointestinal Surgery department, Xinjiang, Urumqi 830000, China.Background: Tumor angiogenesis is essential for colorectal cancer (CRC) progression, providing oxygen and nutrients to sustain tumor growth and metastasis. Protein kinase C iota (Prkci) is an atypical protein kinase known for its oncogenic roles in various cancers; however, its function in CRC angiogenesis remains largely unexplored. This study investigates the role of Prkci in regulating tumor angiogenesis through the Jak2/Stat3 signaling pathway. Methods: Prkci expression levels in CRC tissues and their correlation with micro-vessel density and patient prognosis were analyzed. Functional experiments, including endothelial cell proliferation, migration, and tube formation assays, were performed in vitro to assess the angiogenic effects of Prkci. In vivo, a CRC xenograft mouse model with Prkci knockout was used to evaluate tumor growth and angiogenesis. Mechanistic studies explored how Prkci activates Jak2 by phosphorylating it at the S633 site, leading to downstream Stat3 activation and Vegfa expression. Results: Prkci was upregulated in CRC tissues and correlated with increased micro-vessel density and poor patient prognosis. In vitro, Prkci overexpression enhanced endothelial cell proliferation, migration, and tube formation, while Prkci knockout inhibited these processes. Mechanistically, Prkci phosphorylated Jak2 at S633, leading to enhanced Stat3 activation and increased Vegfa expression, which promoted angiogenesis. In vivo, Prkci knockout in CRC cells significantly reduced tumor growth, angiogenesis, and prolonged survival in a mouse model. Conclusions: These findings identify Prkci as a key regulator of angiogenesis in CRC through Jak2/Stat3 signaling activation. Targeting Prkci could provide a novel therapeutic approach to inhibit tumor angiogenesis and limit CRC progression.http://www.sciencedirect.com/science/article/pii/S1476558625000983PrkciColorectal cancerAngiogenesisJak2/Stat3 pathwayVegfaTherapeutic target |
| spellingShingle | Peng Li Guangshi Liu Wenbin Zhang Tao Li Xinhui Yang Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis Neoplasia: An International Journal for Oncology Research Prkci Colorectal cancer Angiogenesis Jak2/Stat3 pathway Vegfa Therapeutic target |
| title | Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis |
| title_full | Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis |
| title_fullStr | Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis |
| title_full_unstemmed | Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis |
| title_short | Prkci activates Jak2/Stat3 signaling to promote tumor angiogenesis |
| title_sort | prkci activates jak2 stat3 signaling to promote tumor angiogenesis |
| topic | Prkci Colorectal cancer Angiogenesis Jak2/Stat3 pathway Vegfa Therapeutic target |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000983 |
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