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, Escalona, Ruth, Chen, Maoshan, Bilandzic, Maree, Luwor, Rodney, Kannourakis, George, Findlay, Jock, Ahmed, Nuzhat
- Authors: Samardzija, Chantel , Greening, David , Escalona, Ruth , Chen, Maoshan , Bilandzic, Maree , Luwor, Rodney , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. (2017), p. 1-18
- Full Text:
- Reviewed:
- Description: 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. © 2017 The Author(s).
- Authors: Samardzija, Chantel , Greening, David , Escalona, Ruth , Chen, Maoshan , Bilandzic, Maree , Luwor, Rodney , Kannourakis, George , Findlay, Jock , Ahmed, Nuzhat
- Date: 2017
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 7, no. (2017), p. 1-18
- Full Text:
- Reviewed:
- Description: 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. © 2017 The Author(s).
An investigation of the effects of stage of ensilage on Nassella neesiana seeds, for reducing seed viability and injury to livestock
- Weller, Sandra, Florentine, Singarayer, Sillitoe, Jim, Grech, Charles, McLaren, David
- Authors: Weller, Sandra , Florentine, Singarayer , Sillitoe, Jim , Grech, Charles , McLaren, David
- Date: 2016
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 6, no. (2016), p. 1-7
- Full Text:
- Reviewed:
- Description: The noxious weed Nassella neesiana is established on a wide range of productive land throughout southeastern Australia. N. neesiana seeds, when mature, are sharp, causing injury to livestock, thus posing a problem in fodder bales. To reduce infestations of agricultural weeds in situ, production of silage from weed-infested pastures is practised as part of integrated weed management (IWM). However, there is little data to demonstrate whether this process is useful to reduce infestations or the harmful properties of N. neesiana. Therefore, the minimum duration of ensilage required to reduce the viability of N. neesiana seeds was investigated, both with and without addition of ensilage inoculants in this process. Also, the decreasing propensity of the seeds to injure livestock, after various times and conditions of ensilage, was assessed. Ensilage inoculant reduced seed germination probability to zero after 35 days. When no inoculant was added, zero viability was achieved after 42 days. A qualitative assessment of the hardness of ensilaged seeds found seed husks were softer (and therefore safer) after 42 days, whether inoculant was used or not. Therefore, we suggest that both the viability of N. neesiana seeds and hardness of seed casings are significantly reduced after 42 days, thereby reducing the risks of seed dispersal and injury to livestock.
- Authors: Weller, Sandra , Florentine, Singarayer , Sillitoe, Jim , Grech, Charles , McLaren, David
- Date: 2016
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 6, no. (2016), p. 1-7
- Full Text:
- Reviewed:
- Description: The noxious weed Nassella neesiana is established on a wide range of productive land throughout southeastern Australia. N. neesiana seeds, when mature, are sharp, causing injury to livestock, thus posing a problem in fodder bales. To reduce infestations of agricultural weeds in situ, production of silage from weed-infested pastures is practised as part of integrated weed management (IWM). However, there is little data to demonstrate whether this process is useful to reduce infestations or the harmful properties of N. neesiana. Therefore, the minimum duration of ensilage required to reduce the viability of N. neesiana seeds was investigated, both with and without addition of ensilage inoculants in this process. Also, the decreasing propensity of the seeds to injure livestock, after various times and conditions of ensilage, was assessed. Ensilage inoculant reduced seed germination probability to zero after 35 days. When no inoculant was added, zero viability was achieved after 42 days. A qualitative assessment of the hardness of ensilaged seeds found seed husks were softer (and therefore safer) after 42 days, whether inoculant was used or not. Therefore, we suggest that both the viability of N. neesiana seeds and hardness of seed casings are significantly reduced after 42 days, thereby reducing the risks of seed dispersal and injury to livestock.
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