FXYD5 Promotes Metastasis is Mouse Breast Cancer Model

FXYD5 is a member of the FXYD family of proteins. These are short single span transmembrane proteins characterized by the invariant motif Phe-Xxx-Tyr-Asp in their extracellular domain. All members of this group were found to specifically associate with the Na+/K+ ATPase and modulate its kinetic properties. Similar observations have been made for FXYD5 expressed in Xenopus oocytes or mammalian cells. FXYD5 is particularly expressed in the intestinal and lung epithelia, as well as in kidney collecting duct intercalated cells, heart and spleen. Many studies however, have reported additional observations which cannot be readily explained by modulation of transport kinetics.

FXYD5 is overexpressed in various tumors and its expression level correlates with high metastasis and poor prognosis. In a serious of studies using in vitro cell line model systems FXYD5 was shown to inhibit cell adhesion and cell-cell contact, increase cell motility and elevates CCL2 secretion, however there is still little information available on the molecular mechanisms by which FXYD5 affects cancer progression.

The current study aims to demonstrate the putative metastatic effects of FXYD5 and the underlying mechanism(s) in vivo. The model selected was injecting BALB/c mice with syngeneic 4T1 cells derived from BALB/c mammary tumor. Recent results demonstrate that silencing of FXYD5 in the mouse mammary tumor cell line 4T1, largely inhibits tumor growth and metastases induced by injecting these cells into syngeneic mice. I present first in vivo evidence linking FXYD5 to metastasis development and suggest the involvement of Na+/K+ ATPase b­­eta subunit in FXYD5 mediated phenotype.