Breaching and Opening Basement Membrane Barriers: The Anchor Cell Leads the Way

Metastasis is initiated in epithelial-derived tumors when cells at the tumor front breach the epithelial basement membrane (BM). Invasion through BMs is thought to be one of the most rate-limiting steps in cancer progression and thus is a therapeutically attractive target for halting tumor spread. Despite intense interest, it has been challenging to experimentally determine how invasive cells breach and clear BM barriers, which has hindered efforts to block metastasis. Here we discuss how an experimentally tractable developmental invasion event, anchor cell (AC) invasion in the model system C. elegans, is offering powerful new insights into the fundamental mechanisms that invasive cells use to breach BM barriers and how cells at the breach site widen BM gaps through a new mechanism called BM sliding. Finally, we cover studies demonstrating that AC invasion can also be used as a new paradigm to examine how alterations in the tumor microenvironment impinge on cell invasive behavior.