Cilia and Cancer: From Molecular Genetics to Therapeutic Strategies

Abstract

Cilia are microtubule-based organelles that project from the cell surface with motility or sensory functions. Primary cilia work as antennae to sense and transduce extracellular signals. Cilia critically control proliferation by mediating cell-extrinsic signals and by regulating cell cycle entry. Recent studies have shown that primary cilia and their associated proteins also function in autophagy and genome stability, which are important players in oncogenesis. Abnormal functions of primary cilia may contribute to oncogenesis. Indeed, defective cilia can either promote or suppress cancers, depending on the cancer-initiating mutation, and the presence or absence of primary cilia is associated with specific cancer types. Together, these findings suggest that primary cilia play important, but distinct roles in different cancer types, opening up a completely new avenue of research to understand the biology and treatment of cancers. In this review, we discuss the roles of primary cilia in promoting or inhibiting oncogenesis based on the known or predicted functions of cilia and cilia-associated proteins in several key processes and related clinical implications.

Keywords: cancer; cilia; ciliogenesis; ciliome.

Figure 1

Regulation of ciliogenesis by inputs from the cell cycle. Cilium length is indicated by axonemal microtubules (grey rods) bound by the ciliary membrane (orange line) throughout the cell cycle in proliferating cells (S, G2, M, and G1 phases) and during exit into and entry from cell quiescence (G0 phase). Acetyl groups (Acs) shown as grey circles. The various proteins that are discussed in the main text are highlighted in different colors. “P” in a grey circle indicates protein phosphorylation.

Figure 2

Linking ciliome to cancer hallmarks. Distribution of ciliary-related genes and respective signaling pathways among the categories of cancer hallmarks.