The UNC-40(DCC) Receptor Mediates a Morphogenetic Switch that Directs C. elegans Anchor Cell Invasion Across Basement Membrane

Though critical to cancer metastasis, how cells traverse basement membrane (BM) barriers remains poorly understood. We have used time-lapse imaging during C. elegans uterine-vulval connection to capture the entire BM invasion process mediated by the uterine Anchor Cell (AC). We show that the AC breaches the BM by utilizing dynamic actin-rich structures known as invadopodia. When an invadopodium penetrates the BM, it rapidly matures into a stable invasive process that expands the BM breach and crosses into the vulval tissue. We demonstrate that local enrichment of UNC-40 (DCC) presages the site of BM breach and that UNC-40 (DCC) signaling is essential for maturation into an invasive protrusion and the cessation of further invadopodia formation. Using optical highlighting of BM components, we find that rather than relying solely on proteolytic dissolution, the AC’s invasive protrusion also physically displaces BM. These studies provide a comprehensive view of cell-BM interactions during invasion and reveal a key UNC-40-mediated morphogenetic transition that directs invading cells across BM barriers.

Duke Scholars

Author David R. Sherwood Biology