Journal
CELL REPORTS
Volume 24, Issue 4, Pages 962-972Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.06.092
Keywords
-
Categories
Funding
- NIH [R01 CA078461]
- CureMeta
- National Cancer Institute [U01 CA202177]
- NIH/NCI [R01CA218526, 5F31CA189764-03]
- Microenvironmental Influences in Cancer Training Program [NIH/NCIT32CA009592]
- NATIONAL CANCER INSTITUTE [T32CA009592, R01CA078461, U01CA202177, R01CA218526, F31CA189764] Funding Source: NIH RePORTER
Ask authors/readers for more resources
The epithelial-mesenchymal transition (EMT) endows carcinoma cells with traits needed to complete many of the steps leading to metastasis formation, but its contributions specifically to the late step of extravasation remain understudied. We find that breast cancer cells that have undergone an EMT extravasate more efficiently from blood vessels both in vitro and in vivo. Analysis of gene expression changes associated with the EMT program led to the identification of an EMT-induced cell-surface protein, podocalyxin (PODXL), as a key mediator of extravasation in mesenchymal breast and pancreatic carcinoma cells. PODXL promotes extravasation through direct interaction of its intracellular domain with the cytoskeletal linker protein ezrin. Ezrin proceeds to establish dorsal cortical polarity, enabling the transition of cancer cells from a non-polarized, rounded cell morphology to an invasive extravasation-competent shape. Hence, the EMT program can directly enhance the efficiency of extravasation and subsequent metastasis formation through a PODXL-ezrin signaling axis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available