Selective targeting of collagen IV in the cancer cell microenvironment reduces tumor burden.

ABSTRACT: Goodpasture antigen-binding protein (GPBP) is an exportable¹ Ser/Thr kinase that induces collagen IV expansion and has been associated with chemoresistance following epithelial-to-mesenchymal transition (EMT). Here we demonstrate that cancer EMT phenotypes secrete GPBP (mesenchymal GPBP) which displays a predominant multimeric oligomerization and directs the formation of previously unrecognized mesh collagen IV networks (mesenchymal collagen IV). Yeast two-hybrid (YTH) system was used to identify a ²⁶⁰SHCIE²⁶⁴ motif critical for multimeric GPBP assembly which then facilitated design of a series of potential peptidomimetics. The compound 3-[4''-methoxy-3,2'-dimethyl-(1,1';4',1'')terphenyl-2''-yl]propionic acid, or T12, specifically targets mesenchymal GPBP a

SUBMITTER: Revert F 

PROVIDER: S-EPMC5834258 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature