4.4 Article Proceedings Paper

The emerging role of FK506-binding proteins as cancer biomarkers: a focus on FKBPL

Journal

BIOCHEMICAL SOCIETY TRANSACTIONS
Volume 39, Issue -, Pages 663-668

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/BST0390663

Keywords

cancer biomarker; FK506-binding protein (FKBP); FK506-binding protein-like (FKBPL); glucocorticoid receptor (GR); oestrogen; steroid receptor

Funding

  1. BBSRC [BB/I006958/1] Funding Source: UKRI
  2. MRC [G1001473] Funding Source: UKRI
  3. Biotechnology and Biological Sciences Research Council [BB/I006958/1] Funding Source: researchfish
  4. Medical Research Council [G1001473] Funding Source: researchfish
  5. Medical Research Council [G1001473] Funding Source: Medline

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FKBPs (FK506-binding proteins) have long been recognized as key regulators of the response to immunosuppressant drugs and as co-chaperones of steroid receptor complexes. More recently, evidence has emerged suggesting that this diverse protein family may also represent cancer biomarkers owing to their roles in cancer progression and response to treatment. FKBPL (FKBP-like) is a novel FKBP with roles in GR (glucocorticoid receptor), AR (androgen receptor) and ER (oestrogen receptor) signalling. FKBPL binds Hsp90 (heat-shock protein 90) and modulates translocation, transcriptional activation and phosphorylation of these steroid receptors. It has been proposed as a novel prognostic and predictive biomarker, where high levels predict for increased recurrence-free survival in breast cancer patients and enhanced sensitivity to endocrine therapy. Since this protein family has roles in a plethora of signalling pathways, its members represent novel prognostic markers and therapeutic targets for cancer diagnosis and treatment.

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