Publications

Publications

Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients.

J Mol Med (Berl). 2016 Dec;94(12):1411-1422

Wang T, Abou-Ouf H, Hegazy SA, Alshalalfa M, Stoletov K, Lewis J, Donnelly B, Bismar TA

Abstract

Ankyrin G (ANK3) is a member of the Ankyrin family, which functions to provide cellular stability by anchoring the cytoskeleton to the plasma membrane. Deregulation of ANK3 expression has been observed in multiple human cancers but its mechanism remains unknown. ANK3 expression in relation to disease progression and patients’ outcome was investigated in two cohorts of prostate cancer (PCA). Mechanistic studies were carried out in vitro and in vivo using several PCA cell lines and the avian embryo model. Silencing ANK3 resulted in significant reduction of cell proliferation through an AR-independent mechanism. Decreased ANK3 expression delayed S phase to G2/M cell cycle transition and reduced the expression of cyclins A and B. However, cells with knocked-down ANK3 exhibited significant increase in cell invasion through an AR-dependent mechanism. Furthermore, we found that ANK3 is a regulator of AR protein stability. ANK3 knockdown also promoted cancer cell invasion and extravasations in vivo using the avian embryo model (p < 0.01). In human samples, ANK3 expression was dramatically upregulated in high grade intraepithelial neoplasia (HGPIN) and localized PCA (p < 0.0001). However, it was downregulated castration resistant stage (p < 0.0001) and showed inverse relation to Gleason score (p < 0.0001). In addition, increased expression of ANK3 in cancer tissues was correlated with better cancer-specific survival of PCA patients (p = 0.012).

KEY MESSAGE:

Silencing ANK3 results in significant reduction of cell proliferation through an AR-independent mechanism. ANK3 knockdown results in significant increase in cell invasion through an AR-dependent mechanism. ANK3 is a regulator of AR protein stability. ANK3 knockdown also promotes cancer cell invasion and extravasation in vivo using the avian embryo model.

PubMed

Stay Informed

To stay up to date on all the latest news and publications, subscribe to our newsletter!

Prostate Cancer Canada’s Step Up Challenge 2019!

Prostate Cancer Canada’s Step Up Challenge 2019 pits endurance and drive against multistory office tower stairwells and gravity to raise funds for local prostate cancer research projects and initiatives in four Canadian cities. Heroic participants challenged the stairs in Toronto and Calgary on March 3rd, still to come is Vancouver on March 10th and Edmonton on March 17th (St. Patricks day!).

Congratulations to Calgary’s Step Up Challenge event participants who raised 111% of their $95 000 goal! These proceeds will support Dr. Tarek Bismar’s team at the University of Calgary. They are using blood samples from men with slow-growing prostate cancer that has not spread outside the prostate to determine if their disease is likely to advance. Learn more about this project from APCaRI and the Prostate cancer Collaborative Research Alliance.

Edmonton’s Step Up Challenge event is actively raising funds to support Dr. Kerry Courneya’s team at the University of Alberta, with 30% of the $65 000 goal reached currently. Dr. Courneya is a Professor and Canada Research Chair in Physical Activity and Cancer and Director of The Behavioral Medicine Laboratory and Fitness Center. This project is being led by doctoral student Dong-woo (Derek) Kang and will study whether exercise can reduce tumour growth and anxiety for men on active surveillance. Learn more about this project that could contribute to delaying, or even eliminating, the need for treatment from the Behavioral Medicine Laboratory and Fitness Center.

Dr. Kerry Courneya

ERASE-Scientific-Abstract

Please support the Edmonton Step Up Challenge 2019 as either a participant, or donor, or both!
The Lewis lab has entered Team Nanosteps into the challenge, check out our fundraising page and support the team by clicking on this link and making a secure online donation using your credit card.

Kerry Courneya’s Behavioral Medicine Lab team is also hitting the stairs, please click here to go to their Step Up Challenge team page to sponsor them with a donation as well!

Thanks in advance for any support you are able to provide. Get your runners and see you on March 17th!

- Perrin Beatty