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Deciphering Polo Like Kinase-1 Regulated Pathways in Ovarian Cancer

Denison, Linn (2023) MOBN03 20222
Degree Projects in Molecular Biology
Popular Abstract
The Role of Polo Like Kinase-1 in Ovarian Cancer Progression

Ovarian cancer it the most fatal gynecologic cancer, an urgent issue as it is also the eight most common cancer in the global female population. The poor prognosis of the disease is largely attributed to ineffective screening methods, asymptomatic or unspecific disease manifestation, insufficient treatment options and high occurrence of therapy resistance to the conventional chemotherapy in use today. Through understanding and defining molecular signaling pathways in tumour cells which are of importance for cancer growth, we can find new prognostic biomarkers and new targets for medical intervention, which could advance the current treatment as well as increase our... (More)
The Role of Polo Like Kinase-1 in Ovarian Cancer Progression

Ovarian cancer it the most fatal gynecologic cancer, an urgent issue as it is also the eight most common cancer in the global female population. The poor prognosis of the disease is largely attributed to ineffective screening methods, asymptomatic or unspecific disease manifestation, insufficient treatment options and high occurrence of therapy resistance to the conventional chemotherapy in use today. Through understanding and defining molecular signaling pathways in tumour cells which are of importance for cancer growth, we can find new prognostic biomarkers and new targets for medical intervention, which could advance the current treatment as well as increase our understanding of the emergence of ovarian cancer and resistance to therapy.

In this study, we aim to bring light to such unknown molecular pathways regulated by the Polo like kinase-1 (Plk-1), a relevant protein to consider due to its association with cancer aggressiveness and poor survival rates. Although much is known about the role of the protein in promoting cell survival and progression, previous studies indicate that more is to be revealed in terms of molecular signaling pathways involving this protein.

We employed a proximity labeling assay using APEX2, an enzyme effectively tagging neighbouring proteins, which had been linked to the Plk-1 protein. This allowed us to identify interacting proteins in the immediate vicinity of Plk-1, which are expected to be involved in Plk-1 regulated molecular pathways. Through this method, we found an increase of interactions with the protein Forkhead box O3 (FOXO3a) which occurred specifically at the starting point of cell division. FOXO3a is an important protein in the setting of cancer through its partaking in limiting cancer growth. We speculated that Plk-1 could regulate the activity of FOXO3a negatively as a way to maintain continued cell division. Due to this, we decided to look further into apoptosis and autophagy, two molecular processes which impact cell progression and survival and are known to be regulated by both Plk-1 and FOXO3a. This was done by simultaneous inhibition of Plk-1 activity and targeting of components of either process to investigate their relative importance in cell survival. This revealed an ovarian cancer cell type specific dependency on autophagy.

From analysing the protein content of ovarian cancer cells where the activity of Plk-1 was inhibited, we saw indications of connections between the negative regulations of FOXO3a by Plk-1 and a resulting hampering of cell survival. However, this negative regulation and its impact on cancer cell survival could not be fully confirmed through the use of our methods and will need further investigation before definite conclusion can be drawn.

Master’s Degree Project in Molecular Biology, 60 Credits, 2023
Department of Molecular Biology, Lund University
Supervisor: Kazi Julhash Uddin
Department of Laboratory Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Denison, Linn
supervisor
organization
course
MOBN03 20222
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9135720
date added to LUP
2023-08-30 16:33:31
date last changed
2023-08-30 16:33:31
@misc{9135720,
  author       = {{Denison, Linn}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Deciphering Polo Like Kinase-1 Regulated Pathways in Ovarian Cancer}},
  year         = {{2023}},
}