| Abstract |
We previously identified FERM domain containing 4A (FRMD4A) protein as a
human epidermal stem cell marker that is upregulated in head and neck
squamous cell carcinoma (SCC). We now show that FRMD4A is strongly
expressed in SCC, regardless of differentiation status. Knockdown of
FRMD4A decreases growth and metastasis of SCC xenografts in skin and
tongue. It reduces SCC proliferation and intercellular adhesion and
stimulates caspase-3 activity and terminal differentiation. FRMD4A
knockdown causes nuclear accumulation of YAP, indicating a role in Hippo
pathway signalling. Treatment with the HSP90 inhibitor 17-DMAG or ligation
of CD44 with hyaluronan, which cause nuclear depletion of FRMD4A and
nuclear accumulation of YAP, reduce growth and metastasis of SCC
xenografts. We conclude that targeting FRMD4A offers a promising new
approach to treating SCC. Our results show that characterising normal
tissue stem cells can provide unexpected insights into the malignant state.
|
|---|
