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Chasing a cancer suspect to cytokinesis

A potential new way to target aggressive cancers has been identified through a MWC project as part of the research programme investigating genomic approaches to cancer diagnosis and treatment.

Cancer is a major health burden across the globe. In New Zealand, the disease accounts for one in three deaths. One notable characteristic of cancer cells is their ability to continuously divide. This, at least partly, provides them with the potential to endlessly adapt and evolve. Work through MWC is bringing researchers one step closer to halting that endless division.

For 30 years, University of Otago cancer biologist and MWC Principal Investigator Prof Anthony Braithwaite has researched the regulation of cell proliferation, cell survival and the role of p53 protein, one of the most important proteins in cancer biology. In 2015, Prof Braithwaite was granted a prestigious James Cook Research Fellowship from the Royal Society of New Zealand to progress investigation into the lesser understood cold shock Y-box binding protein-1 (YB-1).


A cancer cell undergoing cell division (anaphase shown). The lung cancer cell (A549) has the cytoskeletal protein “Actin” (yellow) stained with a dye and the Y-box binding protein “YB-1” (red) with an antibody. This picture demonstrates the role of YB-1 in a dividing cell. The image was acquired using a 60× oil-immersion objective. Image courtesy of Dr Sunali Mehta.


Supported by MWC funding, Affiliate Investigator Dr Sunali Mehta joined Prof Braithwaites laboratory as a postdoctoral Research Fellow. Here, she gained a deeper understanding of the molecular mechanisms that drive tumour evolution. Sunali and her colleagues have been able to demonstrate the role of YB-1 in cancer progression. The protein is elevated in cancer and associated with very aggressive cancers. The teams findings show YB-1 is a critical regulator of cell division, and that the depletion of YB-1 prevents the formation of daughter cells and this, in turn, limits the growth of cancer cells.

Spurred by these findings and assisted by MWC support to access specialist international facilities, Sunali travelled to Australia, to conduct live cell imaging experiments and next generation sequencing analysis. These experiments, in Dr Anthony Cesare’s laboratory at the Childrens Medical Research Institute in Sydney, allowed her to pinpoint where in the cell cycle YB-1 plays a role. Her work precisely identified the proteins activity during cytokinesis – the last phase as the cell divides into two daughter cells.

Her next tranche of research is exploring YB-1’s role in chromosomal instability.

What we suspect is that YB-1 allows cancer cells to keep changing their DNA content with every cell division. If that is happening, then every time you treat a cancer which has high levels of YB-1, cancer cells can probably continue to evolve by changing chromosome content. The tumour will not respond to the current treatment. It will become resistant. By discovering if this is the mechanism, we could pursue new therapeutics to deal with that phenomenon.”

On the basis of her successful track record with these MWC supported projects, Sunali attained her next career milestone, a promotion to MWC Associate Investigator.

Sunali says she has benefited greatly from the MWC support through her steady career progression, research engagement and discovery, and opportunities for service contribution through the MWC Early Career Researcher Committee. These have now led to major recognition as recipient of a $600,000 Sir Charles Hercus Fellowship in 2021.

Sunali is one of a number of MWC early-career investigators who secured fellowships and awards in 2020 and 2021.  See the awards and honours section on page 84 for details of other recipients.