title: Blockage of PTPRJ promotes cell growth and resistance to 5-FU through activation of JAK1/STAT3 in the cervical carcinoma cell line C33A.
abstract: Gene therapy is a promising therapeutic approach for chemoresistant cervical cancers. Therapeutic interventions targeting the key factors contributing to the initiation and progression of cervical cancer may be a more effective treatment strategy. In the present study, we firstly determined the expression of protein tyrosine phosphatase receptor J (PTPRJ) in 8-paired human cervical tumor and non-tumor tissues. We observed a striking downregulation of PTPRJ in the human cervical tumor tissues. Next, we investigated the roles and the function mechanism of PTPRJ in the human cervical carcinoma cell line C33A by loss- and gain-of-function experiments. Our study indicated that C33A cells with loss of PTPRJ expression showed a significantly increased cell viability, rising growth and migration rate, as well as a G1-S transition. We obtained the opposite results when we overexpressed PTPRJ in C33A cells. Our further study indicated that PTPRJ levels were highly correlated with cell survival when the C33A cells were treated with 5-fluorouracil (5-FU), an important chemotherapeutic agent for cervical cancer. In addition, the signaling pathway screening assay showed an obvious alteration of the Janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) pathway. PTPRJ negatively regulated the activation of the JAK1/STAT3 pathway by decreasing the phosphorylation levels of JAK1 and STAT3. In addition, PTPRJ also regulated the expression of the downstream factors of STAT3, such as cyclin D, Bax, VEGF and MMP2. Our results suggest that PTPRJ may be a promising gene therapy target and its therapeutic potential can be fulfilled when used alone, or in combination with other anticancer agents.
authors: Lanzhou Jiao Tong University Hospital, Lanzhou 730000, P.R. China.
authors: Chun-Mei
authors: CM
authors: Yan
authors: Department of Hematology, Gansu Provincial Hospital, Lanzhou 730000, P.R. China.
authors: Ying-Ling
authors: YL
authors: Zhao
authors: Department of Radiotherapy Oncology, Gansu Provincial Hospital, Lanzhou 730000, P.R. China.
authors: Hong-Yi
authors: HY
authors: Cai
authors: Department of Radiotherapy Oncology, Gansu Provincial Hospital, Lanzhou 730000, P.R. China.
authors: Guo-Ying
authors: GY
authors: Miao
authors: Department of Radiotherapy Oncology, Gansu Provincial Hospital, Lanzhou 730000, P.R. China.
authors: Wen
authors: W
authors: Ma
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002277:Carcinoma / Q000201:enzymology / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004789:Enzyme Activation; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D059585:G1 Phase Cell Cycle Checkpoints; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057809:HEK293 Cells; D006801:Humans; D053613:Janus Kinase 1; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000473:pathology*
chemical_list: D000964:Antimetabolites, Antineoplastic; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D025521:Tumor Suppressor Proteins; C507904:JAK1 protein, human; D053613:Janus Kinase 1; C486288:PTPRJ protein, human; D054631:Receptor-Like Protein Tyrosine Phosphatases, Class 3; D005472:Fluorouracil