Journal
JOURNAL OF CANCER
Volume 7, Issue 13, Pages 1824-1832Publisher
IVYSPRING INT PUBL
DOI: 10.7150/jca.15622
Keywords
Vimentin; Wnt Signaling; EMT; invasion; beta-catenin
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Funding
- National Institutes of Health [NIH RO1CA120895]
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Cancer cell signaling, growth, morphology, proliferation and tumorigenic potential are largely depending on the signaling molecules present naturally in the tumor microenvironment and the identification of key molecules that drive the tumor progression is critical for the development of new modalities for the prevention of tumor progression. High concentrations of vimentin in the blood of cancer patients have been reported, however the function of blood circulating vimentin remains unknown. Here, we investigated the functional role of exogenously supplemented vimentin on colon cancer cells and examined the Wnt Signaling activation and cancer cell invasion. Vimentin when supplemented to the cancer cells remained bound to the surface of the cancer cells. Furthermore, bound vimentin activates Wnt signaling pathway as detectable by increased beta-catenin accumulation in the nucleus with concomitant activation of beta-catenin-dependent transcription of Wnt signaling downstream targets. Functionally, there was an increase in the rate of cellular invasion in these cancer cells upon binding with vimentin. Our results thus suggest that free vimentin in the tumor microenvironment acts as a positive regulator of the beta-catenin signaling pathway, thus providing a basis for cancer invasive properties.
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