Autophagolysosomal exocytosis inverts Src kinase and other N-myristoylated proteins onto the cell surface in cancer

Overexpression of the protoconogene Src is common to a wide variety of
cancers. Here, we demonstrate that Src is noncanonically inverted onto the
cell surface in cancer both in vitro and in vivo. We identify
autophagolysosomal exocytosis (ALE) as a secretory mechanism prominent in
cancer cell lines and show that Src is the prototypical example for a
family of membrane-anchored proteins that are inverted by this process.
Furthermore, we show that this extracellular membrane-associated Src
(eSrc) is present in primary tumors and that anti-Src antibody-based
therapies mediate tumor cell killing in vitro and in vivo. Collectively,
this work presents a secretory mechanism by which intracellular
N-myristoylated proteins, prototypically Src, are inverted on the cell
surface in cancer and can be targeted with antibody therapeutics.