title: Akt2/ZEB2 may be a biomarker for exfoliant cells in ascitic fluid in advanced grades of serous ovarian carcinoma.
abstract: Ovarian cancers present a mild clinical course when diagnosed early but an aggressive pathway when diagnosed in the peri- and postmenopausal periods. However, the predictability of tumor progression is stochastic and is difficult to predict. In the present study, we hypothesized to examine the key pathways that are dysregulated to promote epithelial-mesenchymal transition in serous ovarian carcinoma. Examination of these steps would help to identify ascitic fluid with cells poised for metastasis or otherwise. We focused on examining the Akt2 expression, mainly because of its report as being overamplified in the aggressive variants of ovarian cancer, as well as TGFbeta-sensitivity of Akt2 that forms the key basis for metastasis initiation of most kinds of carcinoma. We obtained primary ovarian carcinoma samples as well as ascitic fluid and distantly metastatic ovarian carcinoma to examine the expression of Akt2. The results of the study demonstrated that in malignant exfoliated ovarian cancer cells, Smad4 expression was tremendously increased in the nuclei, suggesting nuclear translocation of Smad, which thereafter may have activated ZEB2, and thereafter genomically affected the expression of E-cadherin, myosin II, and vimentin, key components for initiating and sustaining metastasis. All of these may have been stimulated by increased cellular expression of Akt2 in metastatic variants of the serous ovarian carcinoma. The reliance on Akt2 and TGF beta signaling may also potentiate the case for Akt inhibitors or small molecule inhibitors of TGFbeta signaling like doxycycline as adjunct chemotherapy in serous ovarian carcinoma, especially the metastatic variants.
authors.affiliation: Department of Obstetrics, Linyi People's Hospital, No.27, East Section, Jiefang Road, Linyi, 276003, China.
authors.forename: Changmei
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Obstetrics, Linyi People's Hospital, No.27, East Section, Jiefang Road, Linyi, 276003, China. FangmeiYang1@126.com.
authors.forename: Fangmei
authors.initials: F
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D024462:Myosin Type II / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051901:Smad4 Protein / Q000096:biosynthesis / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D012097:Repressor Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D053773:Transforming Growth Factor beta1; D014746:Vimentin; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D024462:Myosin Type II
keywords: Ascites; Cancer biomarker; Epithelial-mesenchymal transition; Metastasis; Ovarian carcinoma; Tumor spheroids