, a Novel Transcriptional Target of CD44-Downstream Signaling Promoting Cancer Cell Invasion.

Breast cancer (BC) is the most common malignancy worldwide and has a poor prognosis, because it begins in the breast and disseminates to lymph nodes and distant organs. While invading, BC cells acquire aggressive characteristics from the tumor microenvironment through several mechanisms. Thus, understanding the mechanisms underlying the process of BC cell invasion can pave the way towards the development of targeted therapeutics focused on metastasis.

, a Potential Transcriptional Target Underpinning CD44-Promoted Breast Cancer Progression.

CD44, a cell-adhesion molecule has a dual role in tumor growth and progression; it acts as a tumor suppressor as well as a tumor promoter. In our previous work, we developed a tetracycline-off regulated expression of CD44's gene in the breast cancer (BC) cell line MCF-7 (B5 clone). Using cDNA oligo gene expression microarray, we identified (superoxide dismutase 2) as a potential CD44-downstream transcriptional target involved in BC metastasis.

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

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.