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Full-Text Articles in Cancer Biology
Investigation Of Β5 Integrin Function In Epithelial Ovarian Cancer Cell Adhesion And Metastatic Properties Of Spheroids, Dolly Dhaliwal
Investigation Of Β5 Integrin Function In Epithelial Ovarian Cancer Cell Adhesion And Metastatic Properties Of Spheroids, Dolly Dhaliwal
Electronic Thesis and Dissertation Repository
Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy in the developed world. EOC metastasis is unique since malignant cells detach directly from the primary tumor site into the abdominal fluid and form multicellular aggregates, called spheroids, that possess enhanced survival mechanisms while in suspension. As such, altered cell adhesion properties are paramount to EOC metastasis with cell detachment from the primary tumor, dissemination as spheroids, and reattachment to peritoneal surfaces for secondary tumor formation. These interactions play a crucial role in cell-cell and cell-extracellular matrix interactions, having implications in multiple steps of cancer progression. We previously showed that …
Elucidating The Mechanism Of Nuak1 Function In Ovarian Cancer Metastasis, Jamie Fritz
Elucidating The Mechanism Of Nuak1 Function In Ovarian Cancer Metastasis, Jamie Fritz
Electronic Thesis and Dissertation Repository
Epithelial ovarian cancer (EOC) has a unique mode of metastasis, where upon shedding from the primary tumor, cells form spheroids and spread through the peritoneal cavity. There is a need to elucidate pathways driving spheroid formation to identify novel therapeutic targets. We previously showed that LKB1 is required for EOC metastasis. Using multiplex inhibitor bead-mass spectrometry, we identified NUAK1 as a top LKB1 substrate candidate. We confirmed LKB1 maintains NUAK1 phosphorylation and expression. NUAK1KO cells had lower cell adhesion and generated spheroids with reduced integrity. We identified a cell attachment pathway that was enriched in parental compared with NUAK1 …
Ampk Signalling As A Regulator Of Autophagy In A Model Of Ovarian Tumour Dormancy, Jeremi Laski
Ampk Signalling As A Regulator Of Autophagy In A Model Of Ovarian Tumour Dormancy, Jeremi Laski
Electronic Thesis and Dissertation Repository
One of the hallmarks of epithelial ovarian cancer (EOC) metastasis lies in the process of spheroid formation, whereby tumour cells aggregate into 3D structures. Previous literature suggests that as EOC cells form spheroids they undergo bioenergetic stress, activate AMP-activated protein kinase (AMPK) signaling, and thereby force cells to enter a metabolically quiescent state. We have previously shown that EOC spheroids up- regulate autophagy, a process that provides energy during starvation conditions. Herein, I examined the role of AMPK-mediated signaling regulation of autophagy in a model of ovarian tumour dormancy. Attenuation of AMPK signaling in EOC spheroids resulted in reduction of …
Nuak1 Has Tumor Suppressive Activity In Epithelial Ovarian Cancer, Parima Saxena
Nuak1 Has Tumor Suppressive Activity In Epithelial Ovarian Cancer, Parima Saxena
Electronic Thesis and Dissertation Repository
NUAK1, a downstream substrate of the stress metabolism regulator Liver kinase B1 (LKB1), has been implicated as an oncogene and tumor suppressor, with distinct roles in cell cycle, senescence and cell adhesion. Epithelial ovarian cancer (EOC) spheroids remain dormant during intraperitoneal metastasis with reduced proliferation and metabolism to survive metabolically harsh conditions, possibly implicating a role of NUAK1 in EOC spheroid biology. I hypothesize that NUAK1 is regulated by LKB1 to promote dormancy in EOC. I demonstrate that NUAK1 expression and phosphorylation is regulated by LKB1 in EOC cell lines. NUAK1 is largely under-expressed in many established and new ascites-derived …
Features Of Dormancy In Metastatic Ovarian Cancer Cells, Rohann Jm Correa
Features Of Dormancy In Metastatic Ovarian Cancer Cells, Rohann Jm Correa
Electronic Thesis and Dissertation Repository
The most prevalent subtype of ovarian cancer – high-grade serous (HGS) carcinoma – is also the most lethal, since the majority of cases are characterized by advanced-stage (metastatic) presentation. Metastasis of this cancer proceeds by an intra-peritoneal route, involving detachment of cells from the primary tumour and dissemination throughout the peritoneal cavity as multicellular aggregates, or spheroids. Herein, we demonstrate that HGS patient-derived tumour cells cultured to form in vitro spheroids exhibit features of cancer dormancy, a cellular state known to promote therapeutic resistance and disease recurrence. We discovered that upon spheroid formation, cells became non-proliferative, exhibiting a cell cycle …