Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling

Chantel Samardzija, David W Greening, Ruth Escalona, Maoshan Chen, Maree Bilandzic, Rodney B Luwor, George Kannourakis, Jock K. Findlay, Nuzhat Ahmed

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Article number46312
Number of pages18
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 13 Apr 2017
Externally publishedYes

Cite this

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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.",
author = "Chantel Samardzija and Greening, {David W} and Ruth Escalona and Maoshan Chen and Maree Bilandzic and Luwor, {Rodney B} and George Kannourakis and Findlay, {Jock K.} and Nuzhat Ahmed",
year = "2017",
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day = "13",
doi = "10.1038/srep46312",
language = "English",
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journal = "Scientific Reports",
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publisher = "Nature Publishing Group",

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Knockdown of stem cell regulator Oct4A in ovarian cancer reveals cellular reprogramming associated with key regulators of cytoskeleton-extracellular matrix remodelling. / Samardzija, Chantel; Greening, David W; Escalona, Ruth; Chen, Maoshan; Bilandzic, Maree; Luwor, Rodney B; Kannourakis, George; Findlay, Jock K.; Ahmed, Nuzhat.

In: Scientific Reports, Vol. 7, 46312, 13.04.2017.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Samardzija, Chantel

AU - Greening, David W

AU - Escalona, Ruth

AU - Chen, Maoshan

AU - Bilandzic, Maree

AU - Luwor, Rodney B

AU - Kannourakis, George

AU - Findlay, Jock K.

AU - Ahmed, Nuzhat

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