Poster abstracts
Poster number 58 submitted by Dalton Hironaka
Collagen prolyl 4-hydroxylase mediates disease progression and enzalutamide-resistance in prostate cancer
Dalton Hironaka (Molecular, Cellular, and Developmental Biology Graduate Program), Gaofeng Xiong (Department of Veterinary Biosciences, College of Veterinary Medicine; James Comprehensive Cancer Center)
Abstract:
Prostate cancer (PCa) is the second-leading cause of cancer death
in American men, which is primarily caused by progression to a
treatment-resistant form known as castration-resistant PCa (CRPCa).
CRPCa may be susceptible to treatment with enzalutamide (ENZ), an
androgen receptor antagonist, but resistance can develop due to
compensation by other molecular mechanisms, necessitating the
identification of novel therapeutic targets. In PCa patients, collagen
prolyl 4-hydroxylase subunit α1 (P4HA1) is more highly expressed in
PCa tissues compared to healthy tissues, particularly in metastatic
tissues, and high expression of P4HA1 serves as an adverse
prognostic factor for survival. Our in vitro data show that
overexpression of P4HA1 in CRPCa cell lines is related to castration-
sensitivity. Knockdown of P4HA1 in CRPCa cell lines in vitro
decreases cell invasion and tumorsphere formation while increasing
susceptibility to ENZ in an ENZ-resistant cell line. Together, these
data suggest that overexpression of P4HA1 in PCa contributes to its
progression to CRPCa and mediates resistance to ENZ, making it an
attractive therapeutic target for CRPCa. In future studies, we aim to
use mouse xenograft models of CRPCa to evaluate the contribution
of P4HA1 to tumor growth and metastasis in vivo.
References:
Ito S, Nagata K. Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone.
Semin Cell Dev Biol. 2017 Feb;62:142-151.
Hironaka D., Xiong G*. Enhanced Collagen Prolyl 4-Hydroxylase Activity and Expression
Promote Cancer Progression via Both Canonical and Non-Canonical Mechanisms. Int. J.
Mol. Sci. 2025, 26(19), 9371
Keywords: prostate cancer