MBI PhD Qualifying Exam

Time: 12pm
Date: Tuesday, 27 March 2018
Venue: MBI, level 5 meeting rooms

Supervisors:  Prof Lim Chwee Teck

Role of lamin A/C on the survival of circulating cancer cells traversing capillary-sized constrictions

by JIANG Kuan, Lim Chwee Teck Group

Metastasis is the main cause of death in cancer patients. For cancer cells to metastasize to distant organs, they need to migrate and survive squeezing through narrow intercellular spaces as well as microvessels in the blood circulatory system. However, these confined micro-environments can exert large mechanical deformation and stresses on the circulating cancer cells. Currently, it is not well understood how these physical cues can influence on the subcellular components, and subsequently the fate of these cancer cells. Metastasis has been thought to be an inefficient process as most cancer cells were observed dead in blood circulation and this cell death has been attributed to cell membrane rupture caused by deformation. However, recent studies have revealed that cell nucleus plays a more crucial role during cell traversing through capillary-sized channels. Meanwhile, our recent study showed that breast cancer cells have a poorer survival as compared with their normal epithelial counterparts. Other studies have also shown that cancer cells possess altered nucleus. Hence, we hypothesize that the loss of a nuclear skeleton protein, lamin A/C, in cancer cells is one of the key contributing factors to their poor survival while traversing through microscale constrictions. We will test this hypothesis by investigating the survival of LMNA depleted normal and breast cancer cell lines. In order to further investigate how lamin A/C influences cell survival during large scale deformation, we plan to use NLS-GFP transfected cell lines to characterize the frequency of nuclear rupture events during the transit process and correlate the results with lamin A/C levels. Finally, we will also investigate whether the force transmitted through LINC complex, which is also showed to be dependent on nuclear lamin, during rapid large-scale cell deformation is a factor of nuclear rupture. We envision this project will promote the understanding of how lamin A/C can help resist rapid large scale cell deformation and its effect on metastasis.

**Please note the examination following the seminar is closed-door**