This week we profile a recent publication in Cell Reports from the laboratory of Dr. Shoukat Dedhar (pictured) at UBC.
Can you provide a brief overview of your lab’s current research focus?
The major research focus in my lab at present is to identify molecular vulnerabilities of tumours that lead to resistance to various therapeutic strategies: chemo and radiation, targeted therapetics, and immunotherapy. We have identified tumour microenvironment as well as cancer cell autonomous vulnerabilities, and we are identifying and developing strategies to overcome these resistance mechanisms. We have developed new therapeutics that are being evaluated in pre-clinical models or are in clinical trials for several types of cancers.
What is the significance of the findings in this publication?
In this publication, we describe a very interesting mechanism for the regulation of symmetric versus asymmetric cellular division. The work describes a process whereby mitotic spindle orientation dictates the inheritance of an integrin, α6b1, which is a marker of epithelial stem cells, and provides the growth/division signal. We also identify, for the first time, that Stat3 can regulate mitotic spindle orientation through a non-transcriptional pathway. Stat3 inhibition disrupts mitotic spindle orientation and promotes symmetric division in “normal” epithelial cells, but asymmetric division in tumour-derived cells. These data provide an explanation for the reported function of Stat3 as an oncogene and as a tumour suppressor.
What are the next steps for this research?
Stat3 inhibitors are currently being evaluated in several cancer clinical trials, yet Stat3 has been shown to be critical for the differentiation of normal tissues such as muscle. This work will aid in providing a novel perspective for the use of Stat3 inhibitors, but its also provide novel insights into future research in asymmetric/symmetric cell division.
This work was funded by:
Research in the lab is funded through a CIHR Foundation Scheme grant as well as a Canadian Cancer Society Impact grant.