A pathway required for innate immunity is also required to keep tumorigenic cells alive, report Yuchen Chien, Michael White (University of Texas Southwestern, Dallas, TX), and colleagues.
The RalB GTPase heads one of three pathways downstream of Ras that help drive tumorigenesis (the others are headed by MAP kinase and PI3K). This tumorigenic proliferation often triggers apoptosis. Preventing the apoptosis downstream of RalB, according to the Texas group, is Sec5. (Sec5's partners in secretion are not necessary, however.)
Also required was TBK1, an atypical IκB kinase that was found to bind Sec5. It is better known as part of the innate immune response. Sure enough, viruses induced RalB activity and transcription downstream of TBK1.
Why the connection? Virus-infected cells may stave off death long enough so that they can produce interferons, and this anti-death pathway may have been coopted by cancers. Or the pathway may be used for completely different purposes in the different locations. Either way, says White, the tumorigenesis “makes the [cells] more dependent on a pathway normally not required for survival.” Such conditional dependencies “might be ideal therapeutic targets.”