title: DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis.
abstract: Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo. These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic.
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, NanTong, Jiangsu 226006, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Anatomy, Nantong University, Nantong, JiangSu 226000, People's Republic of China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, NanTong, Jiangsu 226006, People's Republic of China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, NanTong, Jiangsu 226006, People's Republic of China.
authors.forename: Qicheng
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, NanTong, Jiangsu 226006, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Anatomy, Nantong University, Nantong, JiangSu 226000, People's Republic of China.
authors.forename: Jianbing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, NanTong, Jiangsu 226006, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Anatomy, Nantong University, Nantong, JiangSu 226000, People's Republic of China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, NanTong, Jiangsu 226006, People's Republic of China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D015398:Signal Transduction; D000068900:Sitagliptin Phosphate / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C583557:IGF1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D007334:Insulin-Like Growth Factor I; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate
keywords: dipeptidyl peptidase IV; endometrial carcinoma; hypoxia-inducible factor 1a; sitagliptin; vascular endothelial growth factor A