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


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).


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.


Physician in operating room

Recognizing 10 years of philanthropy for prostate cancer research

Working with the Alberta Cancer Foundation and the University of Alberta, the Bird Dogs have enabled a new one-term, five-year chair position to further prostate cancer research — the Bird Dogs Chair in Translational Oncology, a position to be held by researcher Dr. John Lewis. For the last 10 years, Dr. Lewis has held the Frank and Carla Sojonky Chair in Prostate Cancer Research, made possible by a $5 million endowment from the Bird Dogs. Taking over from Dr. Lewis in this position will be surgeon-scientist, Dr. Adam Kinnaird.

“Dr. Lewis’s work in prostate cancer has laid a strong foundation of institutional excellence in the field. Thanks to the generous support of the Bird Dogs and Alberta Cancer Foundation, I look forward to future collaborations between Drs. Kinnaird and Lewis to keep the momentum in world-class prostate cancer research moving forward at the University of Alberta, research that will have immediate impact for Albertans and Canadians with prostate cancer,” says Dr. Brenda Hemmelgarn, Dean of the Faculty of Medicine & Dentistry at the University of Alberta.

As the Bird Dogs Chair in Translational Oncology, Dr. Lewis will focus on driving the clinical translation and commercialization of novel technologies arising from cancer research in Alberta. In partnership with Dr. Kinnaird, the two researchers will collaborate to drive world-class prostate cancer research in Alberta with a common goal of supporting research that helps better understand, diagnose and treat prostate cancer — the most commonly diagnosed cancer in men.

“The Frank and Carla Sojonky Chair in Prostate Cancer Research allows my team to conduct practice-changing clinical trials using state-of-the-art imaging technologies. Because of this funding, we are leading international trials in recruitment and conducting important clinical trials locally to help improve the quality of prostate cancer care for Albertans,” shares Dr. Kinnaird.

During his ten-year tenure as the Frank and Carla Sojonky Chair, Dr. Lewis developed a real-time metastatic imaging model, researched the genetic mechanisms of cancer metastasis, and discovered promising anti-metastatic targets for use as gene therapies, and novel cancer biomarkers for use in biofluid diagnostics. In 2013, with the support of the Bird Dogs and Alberta Cancer Foundation, Dr. Lewis founded the Alberta Prostate Cancer Research Institute (APCaRI), an international collaborative network of prostate cancer scientists, physicians, healthcare employees, and patients. APCaRI’s mission is to accelerate the translation of prostate cancer research from the laboratory to the clinic to improve the lives of men with prostate cancer. Through APCaRI, the Lewis team established a patient data registry and biorepository that has grown into one of the largest prostate cancer databases in the world. Dr. Lewis also founded several spinoff companies including Entos Pharmaceuticals, OncoSenX, and Nanostics to bring innovative therapies and diagnostic tests to patients. Nanostics is currently in the process of launching a simple blood test called ClarityDX Prostate® that can aid in the detection of clinically significant prostate cancer, as the group’s research has shown that using ClarityDX Prostate® as a reflex test vs. the PSA test alone could have resulted in 37 percent fewer unnecessary biopsies.

“The support of the Bird Dogs and the generous community in Alberta has enabled us to develop innovative technologies to help fight prostate cancer,” says Dr. Lewis, Professor, and CEO of Nanostics. “Now, as the new Chair in Translational Oncology, my laboratory will continue to work to develop ways to block the spread of cancer and improve the diagnosis and treatment of prostate cancer for men in Alberta and beyond.”

The Edmonton-based Bird Dogs have passionately supported prostate cancer research for over a decade in memory of the late Frank Sojonky, a businessperson and philanthropist who faced prostate cancer for more than two decades. This year marks 10 years of the Frank & Carla Sojonky Chair in Prostate Cancer Research and the dedicated effort into prostate cancer research.

“We are incredibly grateful to the Bird Dogs and the legacy they have created as well as being the inspiration behind this next evolution of cancer research. Dr. Lewis and Dr. Kinnaird working together will see more discoveries to patients faster and improve the way we treat this cancer and others — not just here in Alberta but around the world,” says Wendy Beauchesne, CEO, Alberta Cancer Foundation

About Nanostics Inc.

Nanostics is a private Alberta-based company focused on the development and commercialization of novel and noninvasive diagnostic tests. Its core technology, ClarityDX®, uses advanced machine learning algorithms to create a disease risk score. ClarityDX® is applicable to a wide range of cancers and other diseases. Nanostics’ lead product, ClarityDX Prostate®, is a test that improves the accuracy of detecting clinically significant prostate cancer. Read more at:

About the Alberta Cancer Foundation

The Alberta Cancer Foundation directly supports the 17 cancer centres across the province, including the new Calgary Cancer Centre and the Tom Baker Cancer Centre in Calgary and Cross Cancer Institute in Edmonton. Our purpose is to create more moments for Albertans facing cancer by inspiring our community to give to innovation in detection, treatment, and care. Thanks to the generosity of our donors we are able to invest in research and care initiatives that will provide real-life returns for Albertans facing cancer. We support every Albertan, no matter what type of cancer they face or where they live in the province.

For media inquiries, contact:

Phoebe Dey
VP Communications & Marketing
Alberta Cancer Foundation
(780) 700-6120

Perrin Beatty, Ph.D.
Communications Lead
Nanostics Inc.

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