Role of primary cilium in pancreatic ductal adenocarcinoma (Review)

Sabanovic, Berina; Giulietti, Matteo; Piva, Francesco

doi:10.3892/ijo.2020.5121

Cited by 3 publications

(3 citation statements)

References 41 publications

(86 reference statements)

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“…The connection between ciliogenesis, the formation of renal cysts, and the development of RCC is supported by a series of evidence published in the last 15 years [66][67][68][69][70][71][72][73]. Indeed, in 2004, Lolkema et al [74] firstly showed that VHL protein can modulate tubulin turnover, thus influencing cellular migration, polarization, and cell-cell interactions.…”

Section: Renal Cell Carcinomamentioning

confidence: 95%

Exploring the Spectrum of Kidney Ciliopathies

Santoni

Piva²,

Cimadamore

et al. 2020

Diagnostics

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Ciliopathies are a group of multi-organ diseases caused by the disruption of the primary cilium. This event leads to a variety of kidney disorders, including nephronophthisis, renal cystic dysplasia, and renal cell carcinoma (RCC). Primary cilium contributes to the regulation of the cell cycle and protein homeostasis, that is, the balance between protein synthesis and degradation by acting on the ubiquitin-proteasome system, autophagy, and mTOR signaling. Many proteins are involved in renal ciliopathies. In particular, fibrocystin (PKHD1) is involved in autosomal recessive polycystic kidney disease (ARPKD), while polycystin-1 (PKD1) and polycystin-2 (PKD2) are implicated in autosomal dominant polycystic kidney disease (ADPKD). Moreover, primary cilia are associated with essential signaling pathways, such as Hedgehog, Wnt, and Platelet-Derived Growth Factor (PDGF). In this review, we focused on the ciliopathies associated with kidney diseases, exploring genes and signaling pathways associated with primary cilium and the potential role of cilia as therapeutic targets in renal disorders.

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Section: Renal Cell Carcinomamentioning

confidence: 95%

Exploring the Spectrum of Kidney Ciliopathies

Santoni

Piva²,

Cimadamore

et al. 2020

Diagnostics

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“…The clinical implications of ciliary genes in PDAC have been recently reviewed [177]. In particular, lower expression of ciliary-associated genes AURKA, PLK1, and NEK2 and higher expression of ciliary-related HDAC6 and INPP5E were associated with favorable prognosis.…”

Section: Gastrointestinal Cancersmentioning

confidence: 99%

“…In particular, the expression profile of AURKA has been associated with a negative prognostic index, as AURKA is overexpressed in tumors of higher histological grade. On the other hand, the overexpression of the cilioprotein INPP5E has been associated with a favorable prognosis [177].…”

Section: Gastrointestinal Cancersmentioning

confidence: 99%

Cilia and Cancer: From Molecular Genetics to Therapeutic Strategies

Carotenuto

Gradilone

Franco

2023

Genes

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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.

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Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling

Niţă

Abraham

Krejčı́

et al. 2021

Cells

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A single primary cilium projects from most vertebrate cells to guide cell fate decisions. A growing list of signaling molecules is found to function through cilia and control ciliogenesis, including the fibroblast growth factor receptors (FGFR). Aberrant FGFR activity produces abnormal cilia with deregulated signaling, which contributes to pathogenesis of the FGFR-mediated genetic disorders. FGFR lesions are also found in cancer, raising a possibility of cilia involvement in the neoplastic transformation and tumor progression. Here, we focus on FGFR gene fusions, and discuss the possible mechanisms by which they function as oncogenic drivers. We show that a substantial portion of the FGFR fusion partners are proteins associated with the centrosome cycle, including organization of the mitotic spindle and ciliogenesis. The functions of centrosome proteins are often lost with the gene fusion, leading to haploinsufficiency that induces cilia loss and deregulated cell division. We speculate that this complements the ectopic FGFR activity and drives the FGFR fusion cancers.

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Role of primary cilium in pancreatic ductal adenocarcinoma (Review)

Cited by 3 publications

References 41 publications

Exploring the Spectrum of Kidney Ciliopathies

Exploring the Spectrum of Kidney Ciliopathies

Cilia and Cancer: From Molecular Genetics to Therapeutic Strategies

Oncogenic FGFR Fusions Produce Centrosome and Cilia Defects by Ectopic Signaling

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