PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway
ObjectiveColorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1026561/full |
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| author | Hong-tao Jia Hong-tao Jia Hong-tao Jia Yan-fei Shao Yan-fei Shao Yan-fei Shao Xue-liang Zhou Xue-liang Zhou Xue-liang Zhou Guang Yang Guang Yang Ling Huang Ling Huang Batuer Aikemu Batuer Aikemu Shu-chun Li Shu-chun Li Cheng-sheng Ding Cheng-sheng Ding Cheng-sheng Ding Xiao-dong Fan Xiao-dong Fan Xiao-dong Fan Hi-ju Hong Hi-ju Hong Sen Zhang Sen Zhang Rui-jun Pan Rui-jun Pan Jing Sun Jing Sun |
| author_facet | Hong-tao Jia Hong-tao Jia Hong-tao Jia Yan-fei Shao Yan-fei Shao Yan-fei Shao Xue-liang Zhou Xue-liang Zhou Xue-liang Zhou Guang Yang Guang Yang Ling Huang Ling Huang Batuer Aikemu Batuer Aikemu Shu-chun Li Shu-chun Li Cheng-sheng Ding Cheng-sheng Ding Cheng-sheng Ding Xiao-dong Fan Xiao-dong Fan Xiao-dong Fan Hi-ju Hong Hi-ju Hong Sen Zhang Sen Zhang Rui-jun Pan Rui-jun Pan Jing Sun Jing Sun |
| author_sort | Hong-tao Jia |
| collection | DOAJ |
| description | ObjectiveColorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into.MethodsThe expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo.ResultsPKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT.ConclusionThe increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT. |
| first_indexed | 2024-04-10T18:06:32Z |
| format | Article |
| id | doaj.art-e07bb65f26fd4090bed1b1617049814f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T18:06:32Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-e07bb65f26fd4090bed1b1617049814f2023-02-02T13:16:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-02-011310.3389/fonc.2023.10265611026561PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathwayHong-tao Jia0Hong-tao Jia1Hong-tao Jia2Yan-fei Shao3Yan-fei Shao4Yan-fei Shao5Xue-liang Zhou6Xue-liang Zhou7Xue-liang Zhou8Guang Yang9Guang Yang10Ling Huang11Ling Huang12Batuer Aikemu13Batuer Aikemu14Shu-chun Li15Shu-chun Li16Cheng-sheng Ding17Cheng-sheng Ding18Cheng-sheng Ding19Xiao-dong Fan20Xiao-dong Fan21Xiao-dong Fan22Hi-ju Hong23Hi-ju Hong24Sen Zhang25Sen Zhang26Rui-jun Pan27Rui-jun Pan28Jing Sun29Jing Sun30Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaObjectiveColorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into.MethodsThe expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo.ResultsPKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT.ConclusionThe increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT.https://www.frontiersin.org/articles/10.3389/fonc.2023.1026561/fullcolorectal cancerprotein kinase C δN-myc downstream-regulated gene 1metastasisepithelial-mesenchymal transition |
| spellingShingle | Hong-tao Jia Hong-tao Jia Hong-tao Jia Yan-fei Shao Yan-fei Shao Yan-fei Shao Xue-liang Zhou Xue-liang Zhou Xue-liang Zhou Guang Yang Guang Yang Ling Huang Ling Huang Batuer Aikemu Batuer Aikemu Shu-chun Li Shu-chun Li Cheng-sheng Ding Cheng-sheng Ding Cheng-sheng Ding Xiao-dong Fan Xiao-dong Fan Xiao-dong Fan Hi-ju Hong Hi-ju Hong Sen Zhang Sen Zhang Rui-jun Pan Rui-jun Pan Jing Sun Jing Sun PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway Frontiers in Oncology colorectal cancer protein kinase C δ N-myc downstream-regulated gene 1 metastasis epithelial-mesenchymal transition |
| title | PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway |
| title_full | PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway |
| title_fullStr | PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway |
| title_full_unstemmed | PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway |
| title_short | PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway |
| title_sort | pkcδ promotes the invasion and migration of colorectal cancer through c myc ndrg1 pathway |
| topic | colorectal cancer protein kinase C δ N-myc downstream-regulated gene 1 metastasis epithelial-mesenchymal transition |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1026561/full |
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