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

Dataset DOI: [10.5061/dryad.z612jm6r4](https://doi.org/10.5061/dryad.z612jm6r4)

## Description of the data and file structure

Files \"Acquisitions_2023-08-03_EK-170_IMP1088_siRNA_anti-Src800_anti-tubulin680.zip 110.88 KB\", \"Acquisitions_2023-08-30_EK190_SRC_siRNA.zip 114.04 KB\", and \"Acquisitions_2023-09-20_EK188_ATG7IN2_and_EK190_SRC_siRNA.zip 245.13 KB\" are fluorescence immunoblots collected on a LiCOR Odyssey CLx (use courtesy of the Renslo Lab at UCSF). In-file metadata have the wrong timestamps due to the fact that the operating computer in the Renslo Lab runs an outdated version of Windows. Dates recorded are listed in the titles. Data are exported by LiCOR's Image Studio 6 as .zip files and can be directly imported into Image Studio Lite (free version) for analysis and processing.

File \"Select_Images_corresponding_to_Figure_3E.zip 366.64 MB\" contains microscopy...,