Cilia and cilia-associated proteins in cancer

Seeger-Nukpezah, Tamina; Little, Joy L.; Serzhanova, Victoria; Golemis, Erica A.

doi:10.1016/j.ddmec.2013.03.004

Cited by 50 publications

(50 citation statements)

References 62 publications

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“…The oncogene Aurora-A is elevated in many cancers. While its primary oncogenic function is often attributed to the role of hyperactive Aurora-A in inducing genomic instability [177], Aurora-A may also contribute to cell transformation by inducing ciliary disassembly [167, 178]. In addition to its other functions noted above, the VHL tumor suppressor also has a role in regulating cilia.…”

Section: Adpkd Beyond the Hallmarks Of Cancermentioning

confidence: 99%

The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease

et al. 2015

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Autosomal dominant polycystic kidney disease (ADPKD) is a progressive inherited disorder in which renal tissue is gradually replaced with fluid-filled cysts, giving rise to chronic kidney disease (CKD) and progressive loss of renal function. ADPKD is also associated with liver ductal cysts, hypertension, chronic pain and extrarenal problems such as cerebral aneurysms. Intriguingly, improved understanding of the signalling and pathological derangements characteristic of ADPKD has revealed marked similarities to those of solid tumours, even though the gross presentation of tumours and the greater morbidity and mortality associated with tumour invasion and metastasis would initially suggest an entirely different disease processes. The commonalities between ADPKD and cancer are provocative, particularly in the context of recent preclinical and clinical studies of ADPKD that have shown promise with drugs that were originally developed for cancer. The potential therapeutic benefit of such repurposing has led us to review in detail the pathological features of ADPKD through the lens of the defined, classic hallmarks of cancer. In addition, we have evaluated features typical of ADPKD, and determined whether evidence supports the presence of such features in cancer cells. This analysis, which places pathological processes in the context of defined signalling pathways and approved signalling inhibitors, highlights potential avenues for further research and therapeutic exploitation in both diseases.

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Section: Adpkd Beyond the Hallmarks Of Cancermentioning

confidence: 99%

The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease

et al. 2015

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“…Emerging evidence has linked defective ciliary disassembly to cancer, and several deciliation factors are known cell cycle regulators that are implicated in tumor growth (Pan et al, 2013;Seeger-Nukpezah et al, 2013). Central amongst these is AURKA, which is activated by most other known deciliation factors (Pan et al, 2013;Seeger-Nukpezah et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Central amongst these is AURKA, which is activated by most other known deciliation factors (Pan et al, 2013;Seeger-Nukpezah et al, 2013). AURKA has been implicated in deciliation in Chlamydomonas (Pan et al, 2004) and retinal pigment epithelial (RPE)1 cells, where AURKA has been shown to be activated by HEF1 to promote activation of HDAC6, causing deacetylation and destabilization of axonemal microtubules (Pugacheva et al, 2007), although the importance of HDAC6 for deciliation has been questioned (Goto et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

PDGFRβ and oncogenic, mutant PDGFRα D842V promote disassembly of primary cilia by a PLCγ and AURKA dependent mechanism

Nielsen

Malinda

Schmid

et al. 2015

Journal of Cell Science

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Primary cilia are microtubule-based sensory organelles projecting from most quiescent mammalian cells, which disassemble in cells cultured in serum-deprived conditions upon re-addition of serum or growth factors. Platelet-derived growth factors (PDGF) are implicated in deciliation, but the specific receptor isoforms and mechanisms involved are unclear. We report that PDGFRβ promotes deciliation in cultured cells and provide evidence implicating PLCγ and intracellular Ca 2+ release in this process. Activation of wild-type PDGFRα alone did not elicit deciliation. However, expression of constitutively active PDGFRα D842V mutant receptor, which potently activates PLCγ (also known as PLCG1), caused significant deciliation, and this phenotype was rescued by inhibiting PDGFRα D842V kinase activity or AURKA. We propose that PDGFRβ and PDGFRα D842V promote deciliation through PLCγ-mediated Ca 2+ release from intracellular stores, causing activation of calmodulin and AURKA-triggered deciliation.

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“…An underlying ciliary dysfunction, due to mutation in BBS genes, is the cause of Bardet-Biedl syndrome with similar phenotype. Current evidence suggests that deregulation of cilia and ciliary dysfunction may correlate closely with cancer through multiple signaling pathways [8].…”

Section: Discussionmentioning

confidence: 99%

Follicular variant of papillary thyroid cancer in Alström syndrome

et al. 2015

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Alström syndrome (AS) is an autosomal recessive disorder, characterized by cone-rod dystrophy, sensorineural hearing loss, obesity, hyperinsulinemia with insulin resistance, type 2 diabetes mellitus and progressive pulmonary, hepatic and renal dysfunction. AS is caused by mutations in the ALMS1 gene, located on the short arm of chromosome 2. We report a 35-year-old woman with known history of AS, who developed a follicular variant of papillary thyroid carcinoma. To our knowledge this is the first association of AS with thyroid malignancy, among the approximately 450 cases reported since the first description of the syndrome. We conclude that papillary thyroid carcinoma should be considered in the differential diagnosis of thyroid nodules in patients with AS.

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Cilia and cilia-associated proteins in cancer

Cited by 50 publications

References 62 publications

The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease

The hallmarks of cancer: relevance to the pathogenesis of polycystic kidney disease

PDGFRβ and oncogenic, mutant PDGFRα D842V promote disassembly of primary cilia by a PLCγ and AURKA dependent mechanism

Follicular variant of papillary thyroid cancer in Alström syndrome

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