KYNU, a novel potential target that underpins CD44-promoted breast tumour cell invasion

Abstract

Using a validated tetracycline-off-inducible CD44 expression system in mouse model, we have previously demonstrated that the hyaluronan (HA) receptor CD44 promotes breast cancer (BC) metastasis to the liver. To unravel the mechanisms that underpin CD44-promoted BC cell invasion, RNA samples were isolated from two cell models: (a) a tetracycline (Tet)-Off-regulated expression system of the CD44s in MCF-7 cells and; (b) as a complementary approach, the highly metastatic BC cells, MDA-MB-231, were cultured in the presence and absence of 50 µg/mL of HA. Kynureninase (KYNU), identified by Microarray analysis, was up-regulated by 3-fold upon induction and activation of CD44 by HA; this finding suggests that KYNU is a potential novel transcriptional target of CD44-downtstream signalling. KYNU is a pyridoxal phosphate (PLP) dependent enzyme involved in the biosynthesis of NAD cofactors from tryptophan that has been associated with the onset and development of BC. This review will attempt to identify and discuss the findings supporting this hypothesis and the mechanisms linking KYNU cell invasion via CD44.

Keywords: KYNU; CD44; Hyaluronan; breast cancer.

FIGURE 1

KYNU pathway involvement in mechanisms associated with tumour development

FIGURE 2

Suggested mechanisms linking HA‐CD44 interaction to KYNU transcription