In a study published in Nature Communications, the group of Alain Chariot, WELBIO investigator at GIGA, Université de Liège, Belgium, identified a new role for the protein KIAA1199 in cervical cancer development resulting from HPV infection.
HPV infection in keratinocytes cause cervical cancer, yet mechanisms by which this oncogenic virus promotes cell survival and proliferation are not totally elucidated. The Chariot laboratory shows that HPV induces the expression of KIAA1199 through BCL-3 and p65, two members of the NF-κB family of transcription factors.
KIAA1199 stabilizes and promotes signaling from EGFR, a receptor whose constitutive activation is linked to cell survival in numerous solid tumors. Moreover, KIAA1199 also limits cell death triggered by molecules such as Semaphorin 3A. The invasive potential of cervical cancer-derived cells also relies on KIAA1199.
Therefore, the results define KIAA1199 as an oncogenic protein induced by HPV infection and constitutive NF-κB activity that transmits pro-survival and invasive signals through EGFR signalling. KIAA1199 may act as an oncogenic in many tumors showing a constitutive EGFR activation.
Shostak et al, NF-κB-induced KIAA1199 promotes survival through EGFR signaling. Nature Communications (2014) doi:10.1038/ncomms6232