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

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2018 APCaRI Fall Symposium

Our fall APCaRI 2018 symposium wrapped up on Saturday afternoon after two days of excellent seminars, great food, lots of coffee, bowling, hikes around Banff, get-togethers at the local pub, and beautiful fall weather with minimal snowfall!

The APCaRI meeting was attended by people from across Canada and the USA representing the Alberta Cancer Foundation, Bird Dogs for Prostate Cancer Research, Cross Cancer Institute, DynaLIFE Medical Labs, Edmonton Health City, Entos Pharmaceuticals, Institute of Health Economics, Nanostics Inc, Northern Alberta Urology Centre, Oisin Biotechnologies, PandiaDX, PROSTAID Calgary, Prostate Cancer Centre, Prostate Cancer Support Group, University of Alberta, University of Calgary, Western University, and the Yukon Hospital Corporation.
The invited speakers gave excellent keynote talks that kick-started interesting conversations during the meeting.

Dr. Alison Allan from Western University gave the Friday keynote seminar on developing circulating tumour cells as liquid biospies for early detection of cancers.

Dr. Melina Cimler, CEO of PandiaDX, and Saturday’s keynote speaker, outlined the potentially complex regulatory pathways that molecular diagnostic companies need to navigate when pursuing regulation in the USA.


Thank you to Rume Djebah for organizing the 2018 APCaRI Fall Symposium!

- Perrin Beatty