EXPLORING THE CROSSTALK BETWEEN POLO-LIKE KINASE 1 AND Eph-FAMILY OF RECEPTORS IN CELL DIVISION IN PANCREATIC CANCER MODEL

Pancreatic cancer (PC) is a lethal disease and have a poor prognosis as well as resistance to chemotherapy and radiation therapy. PC have two subtypes, Pancreatic ductal adenocarcinoma (PDAC) and Pancreatic neuroendocrine tumors (NETs). Between the two subtypes PDAC represent majority of the diagnosed disease with over 90% of the patients. PDAC is an invasive form of PC with an increased rate of cell division as well as more metastatic behaviour. This leads to upregulation of Polo-like kinase 1 (PLK1) a mitotic kinase and Receptor tyrosine kinases (RTKs) which promotes metastatic behaviour. Of the majority of Eph receptors EphA2 is overexpressed in many cancers and in PDAC as well. A wealth of literature has reported an increased expression of PLK1 but therapeutic targeting has not been beneficial and hence an alternative strategies are required to treat PDAC patients. An alternative strategy could be by identifying other gene that is overexpressed in PC patients overexpressing PLK1. One such target is EphA2 as it is overexpressed in many cancers and in PDAC as well. Many of the previous studies have linked EphA2 role in promoting cell migration and regulating metastatic behaviour and only few studies have linked EphA2 role in cell cycle. Through this study we identified the role of EphA2 in high PLK1 PC cells, through computational screening and in vitro assays. We have provided a novel link between PLK1 and EphA2, and how EphA2 regulates cytokinesis through regulating the expression of PLK1. Therefore, inhibiting EphA2 also inhibits PLK1 expression which affects key cytokinetic pathway which ultimately reduced tumour forming capability of high PLK1 PC cells.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Health Sciences

Grantor

University of Saskatchewan

Year dc:date.issued

2023

Author dc:creator

• Patel, Hardikkumar

Committee members dc:contributor.committeemember

• DeCouteau, John
• Uppalapati, Maruti C
• Krishnan, Anand

• Pancreatic cancer, Polo-like kinase 1 (PLK1), Eph receptors

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/10388/15332

OAI identifier oai:identifier

oai:harvest.usask.ca:10388/15332