title: Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients.
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).
  
  
  
  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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Laboratory Services, Calgary, Canada.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Laboratory Services, Calgary, Canada.
authors.forename: Hatem
authors.initials: H
authors.lastname: Abou-Ouf
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Laboratory Services, Calgary, Canada.|The Prostate Cancer Centre, Calgary, AB, Canada.|Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
authors.forename: Samar A
authors.initials: SA
authors.lastname: Hegazy
authors.affiliation: The Prostate Cancer Centre, Calgary, AB, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alshalalfa
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Stoletov
authors.affiliation: Department of Oncology, University of Alberta, Edmonton, AB, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Lewis
authors.affiliation: The Prostate Cancer Centre, Calgary, AB, Canada.|Department of Urology, University of Calgary, Calgary, AB, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: Donnelly
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Laboratory Services, Calgary, Canada. tarek.bismar@cls.ab.ca.|The Prostate Cancer Centre, Calgary, AB, Canada. tarek.bismar@cls.ab.ca.|Departments of Oncology, Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada. tarek.bismar@cls.ab.ca.|Southern Alberta Cancer Research Institute and Tom Baker Cancer Center, Calgary, AB, Canada. tarek.bismar@cls.ab.ca.|Departments of Pathology & Laboratory Medicine and Oncology, Faculty of Medicine, University of Calgary, Rockyview General Hospital, 7007 - 14th Street SW, Calgary, AB, T2V 1P9, Canada. tarek.bismar@cls.ab.ca.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Bismar
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001681:Biological Assay; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002642:Chick Embryo; D015331:Cohort Studies; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011467:Prostate / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D055550:Protein Stability; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: C490613:ANK3 protein, human; C410798:AR protein, human; D017487:Ankyrins; D034741:RNA, Small Interfering; D011944:Receptors, Androgen
keywords: Androgen receptor; Invasion; Lethal disease; Metastasis; Progression; Prostate cancer