KIAA1199 provides a connection between oncogenic signaling of NF-κB and EGFR

Tumor generation and progression are regulated by a series of signaling pathways mediating cell proliferation and survival. EGFR and NF-κB signaling cascades are main pathways involved in those actions. Shostak et al. showed the connection between the two oncogenic cascades by identifying a key factor, KIAA1199, that associated with human papillomavirus (HPV) infection. The article was published on Nature Communications, recently.

Several proteins responsible for oncogenic siganlling of NF-κB, including p50, p65 and BCL-3. Researchers found BCL-3 and p65 were able to induce expression of KIAA1199 in HPV-positive cells and in cervival (pre)neoplastic lesions. Then, KIAA1199 was proved to bind Plexin A2 and counteract Semaphroin 3A-mediated cell death by enhancing stability of EGFR signaling. In addition, researchers found KIAA1199 limited cell apoptosis not only by down-regulating Semaphroin 3A, but also by inactivating Tumour necrosis factor-α (TNFα) pathway, which is negatively regulated by EGFR signaling. Moreover, KIAA1199 up-regulates EGF-mediated epithelial-mesenchymal transition (EMT) in cervical cencer-derived CaSki cells. In summary, this study indicates that KIAA1199, induced by HPV infection, acts as a linker between NF-κB and EGFR signaling pathways in promoting cancer cell proliferation, survival and invasive.

Reference:
Nat Commun. 2014 Nov 4;5:5232.

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