Characterization of NUAK2 pathways and functions in ovarian cancer

Professor Cheung, Annie Nga Yin   (Principal Investigator (PI))

Dr Wong Gee Wan   (Co-Investigator)

Professor Ngan Hextan Yuen Sheung   (Co-Investigator)

30

2022-01-01

1135232

Characterization of NUAK2 pathways and functions in ovarian cancer

ATF4, NUAK2, Ovarian cancer, Unfolded protein response

CancerMolecular Biology

Biology and Medicine (M)

17108421

General Research Fund (GRF)

2021

On-going

1 To delineate the mechanism by which NUAK2 regulates unfolded protein response (UPR) in ovarian cancer cells - Our preliminary data suggested NUAK2 overexpression in ovarian cancer activates the PERK/ATF4 branch of UPR by regulating the ATF4-dependent transcriptional programme and promotes ATF4 nuclear entry under endoplasmic reticulum (ER) stress. It is our primary goal to delineate the mechanisms of this regulation, when and how NUAK2 is involved in UPR of ovarian cancer cells. 2 To evaluate the impact of NUAK2 on metastatic potential and the underlying molecular mechanisms - In our pilot study, a variety of cellular functional effect were observed when NUAK2 was manipulated in in vitro models of ovarian cancer. Among those observations, the impediment of cell migration after NUAK2 knockout was consistent with the finding that metastatic foci of ovarian carcinoma displayed higher expression of NUAK2 than primary tumours. We will focus on studying the impact of NUAK2 on metastatic potential using both in vitro and in vivo models, with the hypothesis that the kinase promotes EMT with evidence obtained from our RNA-seq data. 3 To explore the nuclear function of NUAK2 in ovarian cancer - NUAK2 was reported to be a predominantly nuclear protein as shown in our pilot study. Our finding in clinical ovarian cancer samples demonstrated that, nuclear NUAK2 but not total NUAK2 expression significantly associated with worse prognosis. Little is known about the functional impact of nuclear NUAK2. In this part of study, the DNA binding activity and transcription function of NUAK2 will be characterized. Characterization of the nuclear function of NUAK2 on cell growth, apoptosis, cell invasion and ROS level in the transfected cells under ER stress will be assessed.