2020
DOI: 10.1158/1078-0432.ccr-19-0396
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Targeting the KIF4A/AR Axis to Reverse Endocrine Therapy Resistance in Castration-resistant Prostate Cancer

Abstract: Purpose: Emerging evidence indicates that castration-resistant prostate cancer (CRPC) is often driven by constitutively active androgen receptor (AR) or its V7 splice variant (AR-V7) and commonly becomes resistant to endocrine therapy. The aim of this work is to evaluate the function of a kinesin protein, KIF4A, in regulating AR/AR-V7 in prostate cancer endocrine therapy resistance. Experimental Design: We examined KIF4A expression in clinical prostate cancer specimens by IHC. Regulated pathways were investiga… Show more

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Cited by 37 publications
(33 citation statements)
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“…Kinesin family member 4A (KIF4A) is a highly related gene (Fig. 6 a); it promoted progression in various tumor tissues by regulating chromosome segregation machinery in mediating spindle organization and cytokinesis [ 2 , 5 , 32 ]. A regression analysis using cBioportal showed that KPNA2 and KIF4A levels are highly correlated (Pearson’s correlation = 0.69; Spearman’s correlation = 0.69) (Fig.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…Kinesin family member 4A (KIF4A) is a highly related gene (Fig. 6 a); it promoted progression in various tumor tissues by regulating chromosome segregation machinery in mediating spindle organization and cytokinesis [ 2 , 5 , 32 ]. A regression analysis using cBioportal showed that KPNA2 and KIF4A levels are highly correlated (Pearson’s correlation = 0.69; Spearman’s correlation = 0.69) (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…By mining co-expression and correlation analysis data, we demonstrated that KPNA2 and KIF4A were both overexpressed in ovarian carcinoma. KIF4A, a member of the kinesin superfamily (KIFs), is associated with multiple cellular activities, particularly spindle formation and centrosome assembly in mitosis, chromosome concentration and separation [ 5 , 27 ]. Furthermore, multiple studies have demonstrated that KIF4A is closely correlated with the occurrence and development of various malignancies, such as lung adenocarcinoma [ 34 ], hepatocellular carcinoma [ 15 ], colorectal cancer [ 14 ], prostate cancer [ 5 ].…”
Section: Discussionmentioning
confidence: 99%
“…More and more evidence shows that KIF members are involved in the development and progression of human cancers (36)(37)(38). KIF4A is reported to be abnormally expressed and plays an important role in the progression of various solid cancers (28,39,40).…”
Section: Discussionmentioning
confidence: 99%
“…The expression of AR-V7 was found to be associated with the development of drug resistance (enzalutamide, abiraterone) and aggressive behavior in CRPC cells [ 84 ]. In nude mice harboring human CRPC cell xenografts, treatment with abiraterone significantly increased AR-V7 expression while AR-V7 overexpression promoted tumor growth and invasiveness [ 85 , 86 ]; in line with this observation, targeting this receptor variant was reported to suppress tumor growth and to confer sensitivity to antiandrogens (enzalutamide) [ 87 ]. In humans, the expression of AR-V7 was observed in tumor biopsies from CRPC patients and significantly correlated with tumor progression and short survival [ 88 , 89 , 90 , 91 , 92 ].…”
Section: The Androgen/ar Axis In Crpcmentioning
confidence: 99%