title: PKC iota promotes cellular proliferation by accelerated G1/S transition via interaction with CDK7 in esophageal squamous cell carcinoma.
abstract: Protein kinase C iota (PKCι) has been shown to play an important role in tumorigenesis of many cancers. It was reported that frequent amplification and overexpression of PKCi were correlated with resistance to anoikis in primary esophageal squamous cell carcinomas (ESCC). In this study, we clarified a novel role of PKCι on the cell cycle progression and proliferation in ESCC. Western blot and immunohistochemistry (IHC) analysis showed that the expression of PKCι was higher in ESCC tumor tissues and cell lines. Meanwhile, IHC stain revealed that PKCι was positively correlated with clinical pathologic variables such as tumor size, tumor grade, and tumor invasion, as well as ki67. Immunoprecipitation and immunofluorescence assay revealed that PKCι/CDK7 has the physical interaction and were co-located in the cell nucleus. And this direct interaction could increase the phosphorylation level of CDK7. In vitro studies such as starvation and refeeding assay along with PKCι-shRNA transfection assay demonstrated that PKCι expression promoted proliferation of ESCC cells. And knocking PKCi down by silencing RNA (siRNA) significantly caused cell cycle arrest at G0/G1 phase, decreased rate of colony formation, and alleviated cellular apoptosis. This research provide new insights into PKCi signaling to more deeply understand its cancer-promoting function in ESCC.
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Sujie
authors.initials: S
authors.lastname: Ni
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Shan
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China. zhjg226@sina.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226001, China. nrz0513@sina.cn.
authors.forename: Runzhou
authors.initials: R
authors.lastname: Ni
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D016193:G1 Phase; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016196:S Phase; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D000099293:Protein Kinase C-lambda
chemical_list: D014408:Biomarkers, Tumor; D018844:Cyclin-Dependent Kinases; D007527:Isoenzymes; D011493:Protein Kinase C; D012333:RNA, Messenger; D000099293:Protein Kinase C-lambda
keywords: CDK7; Cell cycle; Esophageal squamous cell carcinoma; PKCι; Proliferation