Ovarian cancer metastasis: The role of ULK1 in downstream signaling in mitochondrial plasticity
Event Type
Research Presentation
Academic Department
Biology
Location
Dana Science Building, 2nd floor
Start Date
26-4-2024 1:30 PM
End Date
26-4-2024 3:00 PM
Description
Ovarian cancer is the deadliest gynecological cancer in women, reported as the fifth leading cause of cancer related deaths in women. With a survival rate of less than 30%, it is a genetically and histologically heterogenous disease and the most aggressive serous ovarian cancer is now thought to originate in the epithelial cells of the fallopian tubes. Ovarian cells exfoliate from their primary tumors and are disseminated throughout peritoneal cavity. Previous studies from our lab show that cancer progression and hypoxic conditions promote reversible changes in mitochondrial morphology in mouse cells and human cell lines that provide the capacity to adapt to the changing tumor microenvironment. Mitochondrial plasticity and mitophagy have been linked as critical events for the survival of disseminating metastases. Ulk1 is a kinase crucial for the activation of autophagy in cells upon exposure to cellular stress like nutrient deprivation or hypoxia. In this study we use mouse models of ovarian cancer progression that represent benign (MOSE-E,) cells, slow-developing (MOSE-L) and fast-developing disease (MOSE-LTICv) to study the impact of mitophagy on cancer cell survival. We aim to generate ULK1 defective ovarian and fallopian tube cell lines to discriminate between the impact of loss of function of ULK1 in cancer cells vs whole body for in vitro and in vivo studies.
Ovarian cancer metastasis: The role of ULK1 in downstream signaling in mitochondrial plasticity
Dana Science Building, 2nd floor
Ovarian cancer is the deadliest gynecological cancer in women, reported as the fifth leading cause of cancer related deaths in women. With a survival rate of less than 30%, it is a genetically and histologically heterogenous disease and the most aggressive serous ovarian cancer is now thought to originate in the epithelial cells of the fallopian tubes. Ovarian cells exfoliate from their primary tumors and are disseminated throughout peritoneal cavity. Previous studies from our lab show that cancer progression and hypoxic conditions promote reversible changes in mitochondrial morphology in mouse cells and human cell lines that provide the capacity to adapt to the changing tumor microenvironment. Mitochondrial plasticity and mitophagy have been linked as critical events for the survival of disseminating metastases. Ulk1 is a kinase crucial for the activation of autophagy in cells upon exposure to cellular stress like nutrient deprivation or hypoxia. In this study we use mouse models of ovarian cancer progression that represent benign (MOSE-E,) cells, slow-developing (MOSE-L) and fast-developing disease (MOSE-LTICv) to study the impact of mitophagy on cancer cell survival. We aim to generate ULK1 defective ovarian and fallopian tube cell lines to discriminate between the impact of loss of function of ULK1 in cancer cells vs whole body for in vitro and in vivo studies.