Van Gogh-Like 2 (VANGL2) is a planar cell polarity protein essential for collective migration during embryonic development, yet its contribution to tumor cell motility and invasion are unknown. We report for the first time that loss of VANGL2 in human cancer cells promotes efficient collective and directed migration and matrix metalloproteinase (MMP)-dependent ECM invasion. We show that VANGL2 knockdown cells exhibit increased activation of secreted MMP2, higher levels of membrane-localized MMP14, and decreased cell-surface fibronectin. These important findings support the notion that planar cell polarity proteins act in coordination with known regulators of cancer cell migration to influence invasion and perhaps metastasis.
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