Autophagolysosomal exocytosis inverts Src kinase onto the cell surface in cancer
Overexpression of the proto-oncogene Src is common to a wide variety of cancers. In this work, we found that Src is noncanonically translocated and inverted onto the cell surface in cancer, both in vitro and in vivo. We identified autophagolysosomal exocytosis (ALE) as a secretory mechanism prominent in cancer cell lines. Src represents the prototypical example of a family of membrane-anchored proteins that are transported by this process. Furthermore, this extracellular membrane-associated Src (eSrc) was found in primary tumors, and anti-Src antibody-based therapies mediated tumor cell killing in cell culture systems and in mouse xenograft models. Thus, intracellular <i>N</i>-myristoylated proteins, prototypically Src, can be topologically inverted onto the cell surface in cancer and targeted with antibody therapeutics.
Authors
- Apurva Pandey (ORCID: https://orcid.org/0000-0001-6944-2518)
- Nancy Greenland (ORCID: https://orcid.org/0000-0002-1783-1711)
- Mark Dennis Evans (ORCID: https://orcid.org/0000-0003-3673-8501)
- Jonathan Chou (ORCID: https://orcid.org/0000-0003-1258-0391)
- Veronica Steri (ORCID: https://orcid.org/0000-0003-2499-6618)
- Fernando Salangsang
- Sima P. Porten (ORCID: https://orcid.org/0000-0002-3948-4968)
- Trenton M. Peters-Clarke (ORCID: https://orcid.org/0000-0002-9153-2525)
- Corleone S. Delaveris (ORCID: https://orcid.org/0000-0002-7291-2338)
- Henry M. Delavan
- R. W. Loudermilk
- J. Vivian Wells
- J. Camara Serrano
- Jesse Ling
- Chunyue Wang
- William J. N. Dougherty
- Soumya G. Remesh
- Chien-Kuang Cornelia Ding
- Kevin K. Leung
- Snehal D. Ganjave
- Carissa E. Chu
Institutions
- University of California, San Francisco (US)
- University of California System (US)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
Publication Details
- Journal
- Science
- Published
- 2026-03-12
- DOI
- https://doi.org/10.1126/science.aec1778
- Citations
- 1
- Primary Topic
- Cellular transport and secretion
- Type
- article
- Field-Weighted Citation Impact
- 23.07