Autophagolysosomal exocytosis inverts Src kinase onto the cell surface in cancer

Science 2026

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Authors: Corleone S. Delaveris, R. W. Loudermilk, Apurva Pandey, Soumya G. Remesh, Trenton M. Peters-Clarke, Snehal D. Ganjave, William J. N. Dougherty, Henry M. Delavan, Chunyue Wang, Jesse Ling, J. Camara Serrano, Fernando Salangsang
+9 more Chien‐Kuang Cornelia Ding, Nancy Greenland, Carissa E. Chu, Sima P. Porten, Veronica Steri, Jonathan Chou, Michael J. Evans, Kevin K. Leung, James A. Wells
DOI: 10.1126/science.aec1778
Cited by: 7
References: 65

Abstract

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 N -myristoylated proteins, prototypically Src, can be topologically inverted onto the cell surface in cancer and targeted with antibody therapeutics.

Fields of Study & Subjects

Cellular transport and secretion Autophagy in Disease and Therapy Erythrocyte Function and Pathophysiology

Publication details

Journal / source
Science
Publisher
American Association for the Advancement of Science (AAAS)
Volume
391
Issue
6790
Pages
eaec1778–eaec1778
Publication date
12 March 2026
Language
EN