IISER Pune
INDIAN INSTITUTE OF SCIENCE EDUCATION AND RESEARCH (IISER) PUNE
where tomorrow’s science begins today
An Autonomous Institution, Ministry of Human Resource Development, Govt. of India
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Seminars and Colloquia

Biology

Challenging pseudo-bipolar divisions in cancer cells with extra centrosomes 
 
Wed, Mar 29, 2017,   04:00 PM to 05:00 PM at Seminar Room 34, 2nd Floor, Main Building

Amitabha Mukhopadhyay, PhD
University of Chicago

The holy grail of chemotherapy is to identify drugs that can selectively recognize and destroy cancer cells while sparing normal cells. A well-known distinction between cancer and normal cells is the number of cellular organelles called, centrosome. While normal cells strictly possess two centrosomes, cancer cells have far too many centrosomes. Centrosomes exquisitely orchestrate the assembly of a sophisticated bipolar cell division apparatus, called the mitotic spindle, for faithful segregation of genetic material between two daughter cells. Although extra centrosomes offer a growth and survival advantage to cancer cells, these overabundant organelles might lead to multipolar spindle formation that is detrimental to cell survival, succumbing to a mitotic/anaphase catastrophe. To escape from the perils of mitotic catastrophe, aggressive cancer cells have evolved ingenious mechanisms to cluster excess centrosomes and assemble a pseudo-bipolar mitotic spindle that is conducive to cell division, thereby allowing cancer cells to survive, thrive and evolve. But, the mechanism of regulation of centrosome number/clustering, and the methods to de-cluster the centrosome is not well known. A hypothesis that is being currently promulgated in the literature suggests that promoting excessive genetic instability could be a potential target for antitumor therapeutics, as tumor cells are programmed to be genetically unstable due to the inactivation of cell-cycle checkpoint pathways. We have demonstrated a mechanism to induce premature mitosis and deplete the aggressive cancer cells of their centrosome-clustering arsenal. This results in highly aberrant multipolar spindles, leading to the catastrophic mitosis that consigns the cancer cells to death.

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