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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APCaRI is part of the Movember Prostate Cancer Outcomes network

The Prostate Cancer Outcomes Global Initiative to Compare and Reduce Variation is a project led by Movember aiming to improve health outcomes for men throughout their prostate cancer journey by focusing on variation in care and engaging clinicians and researchers across 14 countries worldwide.

The international team will collect data from prostate cancer patients segmented into the categories of data items as outlined by the International Consortium for Health Outcomes Measurement (ICHOM). These include patient factors, baseline tumor factors, pathological information, treatment variables, acute complications of treatment, and survival and disease control).

The Alberta Prostate Cancer dataset is highly aligned with the ICHOM standards. This means that we can effectively compare treatments and outcomes in Alberta with teams around the world to find ways to improve our care at home and abroad!

This is the result of hours of planning and true team work lead by Dr. Trafford Crump, the APCaRI Scientific and Data Quality Committee, and the APCaRI clinical, scientific, research and pathology teams. Thanks to your efforts, we are one step closer to improving patient outcomes.

- John Lewis

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Meeting these ambitious goals will not be possible without the committed engagement of our many partners across Alberta, Canada and the World. Learn more about our Partners.