Increase in primary cilia number and length upon VDAC1 depletion contributes to attenuated proliferation of cancer cells.

Primary cilia (PCs) that are present in most human cells and perform sensory function or signal transduction are lost in many solid tumors. Previously, we identified VDAC1, best known to regulate mitochondrial bioenergetics, to negatively regulate ciliogenesis. Here, we show that downregulation of VDAC1 in pancreatic cancer-derived Panc1 and glioblastoma-derived U-87MG cells significantly increased ciliation. Those PCs were significantly longer than the control cells. Such increased ciliation possibly inhibited cell cycle, which contributed to reduced proliferation of these cells. VDAC1-depletion also led to longer PCs in quiescent RPE1 cells. Therefore, serum-induced PC disassembly was slower in VDAC1-depleted RPE1 cells. Overall, this study reiterates the importance of VDAC1 in modulating tumorigenesis, due to its novel role in regulating PC disassembly and cilia length.

Freeing the brake: Proliferation needs primary cilium to disassemble.

Primary cilia are non-motile, microtubule-based, antennae-like organelle that protrude out from the cell surface and perform sensory function or transduce physiological signals in majority of the vertebrate cells. Cilia are assembled on basal bodies that are transformed centrioles. The assembly-disassembly of primary cilia may pose an additional measure on regulating cell cycle in vertebrate cells. While primary cilia are commonly found in differentiated or quiescent cells that are not cycling, disassembly of primary cilia may promote re-entry of these cells into the mitotic cycle, and support proliferation. Many cancer tissues or cancer-derived cells exhibit loss of primary cilia. However, primary cilia may also promote tumorigenesis in some contexts through growth-promoting signalling. This review will shed light on recent advancements of temporal coordination of ciliary disassembly and cell cycle progression, with a focus on how cilia loss may support tumorigenesis in various epithelial cancers.