AURKA

Overview

AURKA (Aurora Kinase A) is a serine/threonine kinase that regulates mitotic entry and centrosome function. In neuroendocrine prostate cancer (NEPC), AURKA is transcriptionally upregulated and cooperates with MYCN to drive neuroendocrine lineage plasticity via the MYCN-CDK5-RB1-E2F1 axis.

Alterations observed in the corpus

  • AURKA expression elevated in NEPC prostate cancer PDXs without gene amplification, linked to neuroendocrine differentiation via the MYCN-CDK5-RB1-E2F1 signaling axis (44 PDXs from 38 patients) PMID:38488813.
  • Copy number alteration (gain) in OSCC; Aurora kinases AURKA and AURKC collectively altered in 14% (5/35) of OSCC tumors (hnsc_mdanderson_2013); drugs in clinical trials noted at time of publication PMID:23619168
  • High RPPA protein expression in the POLE-ultramutated / cell-cycle-deregulated subgroup of endometrial carcinoma (ucec_tcga_pub); co-elevated with ASNS and CCNB1 protein in this subtype PMID:23636398
  • Elevated mitotic-pathway expression implicates AURKA in GS and CIN gastric tumours; nominated as a candidate therapeutic target based on expression profiling PMID:25079317
  • Over-expressed in CRPC-NE (P < 10⁻⁵) and included in the 70-gene NEPC classifier distinguishing castration-resistant neuroendocrine prostate cancer from adenocarcinoma PMID:26855148

Cancer types (linked)

  • PRAD (neuroendocrine subtype) — AURKA overexpression is a hallmark of NEPC and functionally cooperates with MYCN amplification/overexpression to drive neuroendocrine transdifferentiation PMID:38488813.

Co-occurrence and mutual exclusivity

  • AURKA and MYCN are co-elevated in NEPC PDXs; together they activate CDK5, which phosphorylates RB1, releasing E2F1 transcription factors to drive neuroendocrine gene programs PMID:38488813.

Therapeutic relevance

  • PARP inhibition impairs the MYCN-CDK5-RB1-E2F1 axis, which mediates neuroendocrine differentiation, supporting PARP inhibitor investigation in AURKA/MYCN-driven NEPC PMID:38488813.

Open questions

  • AURKA inhibitors (e.g., alisertib) are not directly evaluated in the PDX corpus; the relative contribution of AURKA vs. MYCN upregulation to the NEPC phenotype requires further functional dissection PMID:38488813.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:23619168

This page was processed by crosslinker on 2026-05-09. - PMID:23636398

This page was processed by crosslinker on 2026-05-09. - PMID:25079317

This page was processed by wiki-cli on 2026-05-11. - PMID:26855148

This page was processed by wiki-cli on 2026-05-14.