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

goes to…APCaRI member Russ Greiner

Image of DREAM challenge winners, Russ Greiner pictured on far left.

Dr. Russ Greiner, Canada CIFAR AI Chair, Fellow-in-Residence at Amii, University of Alberta Professor, and APCaRI member, received the CAIAC Lifetime Achievement Award announced at the Canadian AI Conference on May 27, 2021. This the highest honour bestowed by CAIAC, given in recognition to researchers who have distinguished themselves through outstanding research excellence in AI during the course of their academic career. APCaRI congratulates Russ Greiner for his well-deserved CAIAC Lifetime Achievement Award!

“Using machine learning techniques to produce effective, evidence-based personalized treatment”

The main foci of Russ Greiner’s current work are (1) bioinformatics and medical informatics; (2) learning and using effective probabilistic models and (3) formal foundations of learnability. He has published over 200 refereed papers and patents, most in the areas of machine learning and knowledge representation, including 4 that have been awarded Best Paper prizes.

One of these four papers was an entry into an international machine learning competition hosted by DREAM, an open-science effort dedicated to improving health and health care through crowdsourcing problem-solving. DREAM’s challenge was to develop an algorithm to predict which prostate cancer patients would respond to certain treatments and which would follow the medication regimen. The algorithm could be used by clinicians to help chose the best treatment plans for the patient.

Greiner and a team of students tied for the top place in the competition against over 50 teams from around the world. Then the winners collaborated to create an even better solution to the problem!

 

 

 

 

 

 

- Perrin Beatty