title: STYK1 promotes epithelial-mesenchymal transition and tumor metastasis in human hepatocellular carcinoma through MEK/ERK and PI3K/AKT signaling.
abstract: Serine/threonine/tyrosine kinase 1 (STYK1) is known to be involved in tumor progression. However, its molecular role and mechanism in hepatocellular carcinoma (HCC) remains unknown. We evaluated the effect of STYK1 expression in HCC tissues and investigated the underlying mechanisms associated with progression. HCC tissues expressed greater levels of STYK1 than paired non-tumor tissues. Patients with HCC expressing low levels of STYK1 showed both, greater disease-free (p < 0.0001) and overall (p = 0.0004) survival than those expressing high levels of STYK1. Decreased expression of STYK1 was significantly associated with decreased cell proliferation, reduced migratory capability, and reduced invasive capability. Overexpression of STYK1 was significantly associated with increased cell proliferation, migratory capability, and invasive capability in vitro, as well as increased volume of tumor, weight of tumor, and number of pulmonary metastases in vivo. Furthermore, STYK1's mechanism of promoting cancer cell mobility and epithelial-mesenchymal transition (EMT) was found to be via the MEK/ERK and PI3K/AKT pathways, resulting in increased expression of mesenchymal protein markers: snail, fibronectin, and vimentin, and decreased E-cadherin expression. Our results suggest that STYK1 acts as an oncogene by inducing cell invasion and EMT via the MEK/ERK and PI3K/AKT signaling pathways and it therefore may be a potential therapeutic target in HCC.
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Deng
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Shaohan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liao
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; C482299:STYK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases