1. T-LAK cell-originated protein kinase (TOPK) enhances androgen receptor splice variant (ARv7) and drives androgen-independent growth in prostate cancer.
- Author
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Alhawas, Lama, Amin, Karishma S, Salla, Bharath, and Banerjee, Partha P
- Subjects
PROTEIN kinases ,CASTRATION-resistant prostate cancer ,PROSTATE cancer ,ANDROGEN receptors ,TUMOR growth ,ABIRATERONE acetate ,CANCER invasiveness - Abstract
Despite impressive advances in the treatment of prostate cancer with various efficacious inhibitors along the androgen/androgen receptor axis, eventual development of incurable metastatic Castration-Resistant Prostate Cancer (mCRPC) is inevitable and remains a major clinical challenge. Constitutively active androgen receptor (AR) spliced variants have emerged as primary means of resistance to anti-androgens and androgen synthesis inhibitors. The alternatively spliced AR variant, ARv7, has attracted significant interest due to its constitutively active status in CRPC that drives androgen-independence. Factors that are involved in regulating ARv7 levels in CRPC are not clearly known. We recently demonstrated that a protein kinase, T-LAK cell-originated protein kinase (TOPK) level correlates with the aggressiveness of prostate cancer and its invasive behavior. In this study, we investigated whether TOPK plays a role in driving androgen-independence in prostate cancer cells. Our data demonstrate that TOPK overexpression in androgen-dependent LNCaP and VCaP induces ARv7 and drives androgen-independent growth. On the other hand, pharmacological inhibition of TOPK in androgen-independent LNCaP95 and 22Rv1 represses AR transactivation, and AR stability. In summary, this study illustrates a direct role of TOPK in regulating ARv7 and driving androgen-independence in prostate cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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