Ciliary signalling in cancer

Abstract

Although tumours initiate from oncogenic changes in a cancer cell, subsequent tumour progression and therapeutic response depend on interactions between the cancer cells and the tumour microenvironment (TME). The primary monocilium, or cilium, provides a spatially localized platform for signalling by Hedgehog, Notch, WNT and some receptor tyrosine kinase pathways and mechanosensation. Changes in ciliation of cancer cells and/or cells of the TME during tumour development enforce asymmetric intercellular signalling in the TME. Growing evidence indicates that some oncogenic signalling pathways as well as some targeted anticancer therapies induce ciliation, while others repress it. The links between the genomic profile of cancer cells, drug treatment and ciliary signalling in the TME likely affect tumour growth and therapeutic response.

Mixed signals from the cell's antennae: primary cilia in cancer

“…In line of the reported restriction of active Hh signaling in the stromal compartment of pancreatic cancer tissues, the authors promote a model that PC regulate Hh signaling in the stromal tumor environment, which is in agreement with observations made by Bailey et al [97]. In this context, we would like to refer to an excellent review that was published during preparation of this manuscript describing in detail the role of PC in the crosstalk between cancer cells and their microenvironment [102].…”

Misactivation of Hedgehog signaling causes inherited and sporadic cancers

“…Pancreatic ductal adenocarcinoma (PDAC) is associated with upregulation of SHH, but in mice, SMO is dispensable for PDAC growth, suggesting that misactivation of the HH pathway is not a critical driver of this cancer either (141,142). Moreover, unlike BCC and medulloblastoma, PDAC is associated with loss of cilia (143,144), providing ancillary evidence that the normal HH pathway is not hyperactivated in PDAC. However, PDAC stromal cells, such as fibroblasts and endojci.org Volume 129 Number 2 February 2019 thelial cells, respond to SHH produced by tumor cells, suggesting that paracrine signaling may modulate PDAC progression (145)(146)(147).…”

Differentiation of ciliated human midbrain-derived LUHMES neurons

“…Primary cilia are antennae that receive and transduce signals from the immediate environment of a cell. The primary cilium as a signaling hub integrates several aspects of the SHH pathway, but is also involved in other signal transduction pathways, such as WNT, Notch, platelet-derived growth factor (PDGF) or multiple G-protein coupled receptors (Goetz and Anderson, 2010; Lauter et al, 2018; Liu et al, 2018; Wheway et al, 2018). In addition to being a receiver, the primary cilium has also gained attention as a source of signals to its cellular environment (Garcia et al, 2018; Nachury and Mick, 2019).…”