| Autor: |
Samardzija C; Department of Obstetrics and Gynaecology, University of Melbourne, Victoria 3052, Australia., Greening DW; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia., Escalona R; 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., Chen M; Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia., Bilandzic M; The Hudson Institute of Medical Research, Victoria 3168, Australia., Luwor R; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, Victoria 3052, Australia., Kannourakis G; Fiona Elsey Cancer Research Institute, Ballarat, Victoria 3353, Australia.; Federation University Australia, Ballarat, Victoria 3010, Australia., Findlay JK; Department of Obstetrics and Gynaecology, University of Melbourne, Victoria 3052, Australia.; The Hudson Institute of Medical Research, Victoria 3168, Australia., Ahmed N; 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. |
| Abstrakt: |
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. |
