Table of Contents
Cancers, Volume 11, Issue 7 (July 2019)
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Cover Story (view full-size image) Oncogenic RAS is a major driver of cancer cell proliferation and dysregulation of cell signaling. [...] Read more. Oncogenic RAS is a major driver of cancer cell proliferation and dysregulation of cell signaling. The existing paradigm teaches us that it is propagated through cell division (vertical transmission). We proposed horizontal intercellular transport of oncogenic KRAS via tunneling nanotubes (TNTs) as a unique mechanism of inducing intracellular mutational heterogeneity in colon cancer cells. We discovered that TNTs are upregulated in colon cancer cells harboring mutant KRAS and deficits in mismatch repair. Furthermore, wild-type KRAS colon cancer cells that acquired mutant KRAS demonstrated increased formation of TNTs, which in turn promoted intercellular transfer of oncogenic KRAS. We propose that cell-to-cell transfer of mutant RAS is a novel form of communication that can potentially induce intracellular and, on a larger tumor microenvironmental scale, intratumoral heterogeneity. View this pa