Role of the NFκB-signaling pathway in cancer

Abstract

Cancer is a group of cells that malignantly grow and proliferate uncontrollably. At present, treatment modes for cancer mainly comprise surgery, chemotherapy, radiotherapy, molecularly targeted therapy, gene therapy, and immunotherapy. However, the curative effects of these treatments have been limited thus far by specific characteristics of tumors. Abnormal activation of signaling pathways is involved in tumor pathogenesis and plays critical roles in growth, progression, and relapse of cancers. Targeted therapies against effectors in oncogenic signaling have improved the outcomes of cancer patients. NFκB is an important signaling pathway involved in pathogenesis and treatment of cancers. Excessive activation of the NFκB-signaling pathway has been documented in various tumor tissues, and studies on this signaling pathway for targeted cancer therapy have become a hot topic. In this review, we update current understanding of the NFκB-signaling pathway in cancer.

Keywords: cancer; inflammation; nuclear factor kappa-B; p65; signaling pathway.

Figure 1

Structure of NFκB members. Notes: The NFκB family consists of three proteins with a transactivation domain (RelA [p65], cRel, and RelB) and two proteins lacking a transactivation domain (p105/p50 and p100/p52). Similarly, only p105/p50 and p100/p52 have ankyrin repeats that function as p52 and p50 inhibitors. However, all these proteins share an Rel-homology domain, associated with DNA binding, dimerization, nuclear localization and IκB binding, and nuclear localization signal exposure, which is vital to the translocation of the dimer into the nucleus. Abbreviation: NIK, NFκB-inducing kinase.

Figure 2

Activation of NFκB cascade by the classical/canonical signaling pathway (right) and alternative/noncanonical signaling pathway (left). Abbreviations: NLS, nuclear localization sequence; RHD, Rel-homologous domain; TAD, transactivation domain.