Choreographing Metastasis to the Tune of LTBP

Latent Transforming Growth Factor beta (TGF beta) Binding Proteins (LTBPs) are chaperones and determinants of TGF beta isoform-specific secretion. They belong to the LTBP/Fibrillin family and form integral components of the fibronectin and microfibrillar extracellular matrix (ECM). LTBPs serve as master regulators of TGF beta bioavailability, functioning to incorporate and spatially pattern latent TGF beta at regular intervals within the ECM, and actively participate in integrin-mediated stretch activation of TGF beta in vivo. In so doing they create a highly patterned sensory system where local changes in ECM tension can be detected and transduced into focal signals. The physiological role of LTBPs in the mammary gland remains largely unstudied, however both loss and gain of LTBP expression is found in breast cancers and breast cancer cell lines. Importantly, elevated LTBP1 levels appear in two gene signatures predictive of enhanced metastatic behavior. LTBP may promote metastasis by providing the bridge between structural and signaling components of the epithelial to mesenchymal transition (EMT).