title: Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling.
abstract: Oct4A is a master regulator of self-renewal and pluripotency in embryonic stem cells. It is a well-established marker for cancer stem cell (CSC) in malignancies. Recently, using a loss of function studies, we have demonstrated key roles for Oct4A in tumor cell survival, metastasis and chemoresistance in in vitro and in vivo models of ovarian cancer. In an effort to understand the regulatory role of Oct4A in tumor biology, we employed the use of an ovarian cancer shRNA Oct4A knockdown cell line (HEY Oct4A KD) and a global mass spectrometry (MS)-based proteomic analysis to investigate novel biological targets of Oct4A in HEY samples (cell lysates, secretomes and mouse tumor xenografts). Based on significant differential expression, pathway and protein network analyses, and comprehensive literature search we identified key proteins involved with biologically relevant functions of Oct4A in tumor biology. Across all preparations of HEY Oct4A KD samples significant alterations in protein networks associated with cytoskeleton, extracellular matrix (ECM), proliferation, adhesion, metabolism, epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and drug resistance was observed. This comprehensive proteomics study for the first time presents the Oct4A associated proteome and expands our understanding on the biological role of this stem cell regulator in carcinomas.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne, Victoria 3052, Australia.
authors.forename: Chantel
authors.initials: C
authors.lastname: Samardzija
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Greening
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne, Victoria 3052, Australia.|The Hudson Institute of Medical Research, Victoria 3168, Australia.|Fiona Elsey Cancer Research Institute, Ballarat, Victoria 3353, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Escalona
authors.affiliation: Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia.
authors.forename: Maoshan
authors.initials: M
authors.lastname: Chen
authors.affiliation: The Hudson Institute of Medical Research, Victoria 3168, Australia.
authors.forename: Maree
authors.initials: M
authors.lastname: Bilandzic
authors.affiliation: Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Victoria 3052, Australia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Luwor
authors.affiliation: Fiona Elsey Cancer Research Institute, Ballarat, Victoria 3353, Australia.|Federation University Australia, Ballarat, Victoria 3010, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Kannourakis
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne, Victoria 3052, Australia.|The Hudson Institute of Medical Research, Victoria 3168, Australia.
authors.forename: Jock K
authors.initials: JK
authors.lastname: Findlay
authors.affiliation: Department of Obstetrics and Gynaecology, University of Melbourne, Victoria 3052, Australia.|The Hudson Institute of Medical Research, Victoria 3168, Australia.|Fiona Elsey Cancer Research Institute, Ballarat, Victoria 3353, Australia.|Federation University Australia, Ballarat, Victoria 3010, Australia.
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000172:deficiency*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
chemical_list: D015415:Biomarkers; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D020543:Proteome