Tetraspanins are a family of small
proteins that interact with themselves, host transmembrane and cytosolic
proteins to form
tetraspanin enriched microdomains (TEMs) that regulate important cellular functions. Several
tetraspanin family members are linked to
tumorigenesis.
Hepatocellular carcinoma (HCC) is an increasing global health burden, in part due to the increasing prevalence of hepatitis C virus (HCV) associated HCC. The
tetraspanin CD81 is an essential receptor for HCV, however, its role in
hepatoma biology is uncertain. We demonstrate that antibody engagement of CD81 promotes
hepatoma spread, which is limited by HCV
infection, in an actin-dependent manner and identify an essential role for the C-terminal interaction with
Ezrin-
Radixin-
Moesin (ERM)
proteins in this process. We show enhanced
hepatoma migration and invasion following expression of CD81 and a reduction in invasive potential upon CD81 silencing. In addition, we reveal poorly differentiated HCC express significantly higher levels of CD81 compared to adjacent non-
tumor tissue. In summary, these data support a role for CD81 in regulating
hepatoma mobility and propose CD81 as a tumour promoter.