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Page 17 of 36 J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21

Biography
Silvia Martina Ferrari is graduated in Biological Sciences cum laude in 2002 and specialized in Clinical
Pathology in 2007 at the University of Pisa (Italy). Her principal areas of expertise are autoimmune thyroid
disorders, chemokines and cytokines, type 1 diabetes, systemic autoimmune disorders, HCV-associated
thyroid disorders and thyroid cancer. Her researches have been published in more than 158 articles on
International journals (HI = 38). She serves as an editorial board member and is Referee and Reviewer of
many scientific International journals.

21. Mitochondrial dynamics and chemoresistance in ovarian cancer

1
Youngjin Han , Yong Sang Song 1,2

1 Cancer Research Institute, Seoul National University, Seoul 03080, South Korea.
2 Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul 03080,
South Korea.

Various cellular and acellular components constitute tumor microenvironment affecting metabolism
and malignant phenotypes of cancer. Hypoxia and increased level of reactive oxygen species (ROS) are
frequently observed in many types of malignant tissues composed of cancer cells and surrounding tumor
microenvironment, including ovarian cancer. In response to the increased level of ROS, cancer cells
activate antioxidant mechanisms to counterbalance increased ROS. PGC1α is a key molecule critical
for mitochondrial biogenesis and upregulation of antioxidant enzymes. In our previous research, we
reported that PGC1α is associated with cisplatin-resistance in tumor spheres. Tumor sphere cells acquired
stem cell-like properties together with increased production of ROS. ROS was shown to be important
for maintaining stemness and PGC1α expression of the tumor sphere cells in ovarian cancer. Decreased
sensitivity to cisplatin was observed in both tumor sphere and PGC1α-overexpressing cells, while silencing
PGC1α sensitized the tumor sphere cells to cisplatin. Along with upregulation of PGC1α expression in
tumor sphere cells, mitochondrial fission was increased in comparison to their parental cells. Similar to
the in-vivo environment of the malignant tumor, tumor spheres exhibit hypoxia at the core. The center
of tumor spheres is exposed to hypoxia like in vivo tumor. As the tumor sphere grows larger in size, a
hypoxic gradient towards the core of the sphere is created. Next, we investigated the effect of hypoxia on
mitochondrial dynamics. Mitochondria, dynamic intracellular organelles, go through incessant processes
of fission/fusion and biogenesis by various stimuli in tumor microenvironment. Under hypoxic (< 1 % O2)
culture conditions, mitochondrial fission was increased together with increased resistance to cisplatin in
ovarian cancer cells. Inhibition of mitochondrial fission enhanced sensitivity of cancer cells to cisplatin.
Our findings suggest that PGC1α-induced mitochondrial biogenesis and alteration of mitochondrial
dynamics by hypoxia could cause the cisplatin resistance of ovarian cancer cells. The changes in
mitochondrial biogenesis and dynamics of cancer cells adapted to tumor microenvironment could be a
novel therapeutic target to overcome chemoresistance in ovarian cancer.

Biography
Prof. Yong Sang Song is with the Department of Obstetrics and Gynecology, College of Medicine, Seoul
National University, Korea. He received MD, College of Medicine, Seoul National University, Korea from
1977 to 1983; the MS and the PhD, Postgraduate School Seoul National University, Korea. His major
interests are molecular mechanisms of tumors, especially the role of tumor microenvironment in cancer cell
metabolism and chemoresistance and precision medicine in ovarian cancer. He is particularly interested in
the impacts of components of tumor microenvironment in ovarian cancer progression. He has published
more than 300 papers in the science citation index journals.