Identification and characterization of primary cilia-positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation.
ARL13B
Hedgehog signalling pathway
TTBK2
adenoid cystic carcinoma
basal cell adenocarcinoma
basal cell adenoma
basaloid/myoepithelial differentiation
primary cilia
salivary gland tumour
Journal
The Journal of pathology
ISSN: 1096-9896
Titre abrégé: J Pathol
Pays: England
ID NLM: 0204634
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
20
04
2021
received:
04
03
2021
accepted:
27
04
2021
pubmed:
2
5
2021
medline:
1
1
2022
entrez:
1
5
2021
Statut:
ppublish
Résumé
Primary cilia (PC) are non-motile, antenna-like structures on the cell surface. Many types of neoplasms exhibit PC loss, whereas in some neoplasms PC are retained and involved in tumourigenesis. To elucidate the PC status and characteristics of major salivary gland tumours (SGTs), we examined 100 major SGTs encompassing eight histopathological types by immunohistochemical analysis. PC were present in all (100%) of the pleomorphic adenomas (PAs), basal cell adenomas (BCAs), adenoid cystic carcinomas (AdCCs), and basal cell adenocarcinomas (BCAcs) examined, but absent in all (0%) of the Warthin tumours, salivary duct carcinomas, mucoepidermoid carcinomas, and acinic cell carcinomas examined. PC were also detected by electron-microscopic analysis using the NanoSuit method. It is worthy of note that the former category and latter category of tumours contained and did not contain a basaloid/myoepithelial differentiation component, respectively. The four types of PC-positive SGTs showed longer PC than normal and exhibited a characteristic distribution pattern of the PC in the ductal and basaloid/neoplastic myoepithelial components. Two PC-positive carcinomas (AdCC and BCAc) still possessed PC in their recurrent/metastatic sites. Interestingly, activation of the Hedgehog signalling pathway, shown by predominantly nuclear GLI1 expression, was significantly more frequently observed in PC-positive SGTs. Finally, we identified tau tubulin kinase 2 (TTBK2) as being possibly involved in the production of PC in SGTs. Taken together, our findings indicate that SGTs that exhibit basaloid/myoepithelial differentiation (PA, BCA, AdCC, and BCAc) are ciliated, and their PC exhibit tumour-specific characteristics, are involved in activation of the Hedgehog pathway, and are associated with TTBK2 upregulation, providing a significant and important link between SGT tumourigenesis and PC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Substances chimiques
Hedgehog Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
519-530Informations de copyright
© 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Références
Bangs F, Anderson KV. Primary cilia and mammalian Hedgehog signaling. Cold Spring Harb Perspect Biol 2017; 9: a028175.
Mitchison HM, Valente EM. Motile and non-motile cilia in human pathology: from function to phenotypes. J Pathol 2017; 241: 294-309.
Nishimura Y, Kasahara K, Shiromizu T, et al. Primary cilia as signaling hubs in health and disease. Adv Sci (Weinh) 2019; 6: 1801138.
Wheway G, Nazlamova L, Hancock JT. Signaling through the primary cilium. Front Cell Dev Biol 2018; 6: 8.
Bashford AL, Subramanian V. Mice with a conditional deletion of Talpid3 (KIAA0586) - a model for Joubert syndrome. J Pathol 2019; 248: 396-408.
Reiter JF, Leroux MR. Genes and molecular pathways underpinning ciliopathies. Nat Rev Mol Cell Biol 2017; 18: 533-547.
Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008; 22: 2454-2572.
Taipale J, Cooper MK, Maiti T, et al. Patched acts catalytically to suppress the activity of Smoothened. Nature 2002; 418: 892-897.
Corbit KC, Aanstad P, Singla V, et al. Vertebrate Smoothened functions at the primary cilium. Nature 2005; 437: 1018-1021.
Kogerman P, Grimm T, Kogerman L, et al. Mammalian Suppressor-of-Fused modulates nuclear-cytoplasmic shuttling of Gli-1. Nat Cell Biol 1999; 1: 312-319.
Doheny D, Manore SG, Wong GL, et al. Hedgehog signaling and truncated GLI1 in cancer. Cells 2020; 9: 2114.
Seeley ES, Carrière C, Goetze T, et al. Pancreatic cancer and precursor pancreatic intraepithelial neoplasia lesions are devoid of primary cilia. Cancer Res 2009; 69: 422-430.
Gradilone SA, Radtke BN, Bogert PS, et al. HDAC6 inhibition restores ciliary expression and decreases tumor growth. Cancer Res 2013; 73: 2259-2270.
Kim J, Dabiri S, Seeley ES. Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma. PLoS One 2011; 6: e27410.
Hassounah NB, Nagle R, Saboda K, et al. Primary cilia are lost in preinvasive and invasive prostate cancer. PLoS One 2013; 8: e68521.
Schraml P, Frew IJ, Thoma CR, et al. Sporadic clear cell renal cell carcinoma but not the papillary type is characterized by severely reduced frequency of primary cilia. Mod Pathol 2009; 22: 31-36.
Egeberg DL, Lethan M, Manguso R, et al. Primary cilia and aberrant cell signaling in epithelial ovarian cancer. Cilia 2012; 1: 15.
Ho L, Ali SA, Al-Jazrawe M, et al. Primary cilia attenuate hedgehog signalling in neoplastic chondrocytes. Oncogene 2013; 32: 5388-5396.
Menzl I, Lebeau L, Pandey R, et al. Loss of primary cilia occurs early in breast cancer development. Cilia 2014; 3: 7.
Eguether T, Hahne M. Mixed signals from the cell's antennae: primary cilia in cancer. EMBO Rep 2018; 19: e46589.
Wong SY, Seol AD, So PL, et al. Primary cilia can both mediate and suppress Hedgehog pathway-dependent tumorigenesis. Nat Med 2009; 15: 1055-1061.
Han YG, Kim HJ, Dlugosz AA, et al. Dual and opposing roles of primary cilia in medulloblastoma development. Nat Med 2009; 15: 1062-1065.
Girardi D, Barrichello A, Fernandes G, et al. Targeting the Hedgehog pathway in cancer: current evidence and future perspectives. Cells 2019; 8: 153.
Coy S, Du Z, Sheu SH, et al. Distinct patterns of primary and motile cilia in Rathke's cleft cysts and craniopharyngioma subtypes. Mod Pathol 2016; 29: 1446-1459.
Iruzubieta P, Monzón M, Castiella T, et al. Hedgehog signalling pathway activation in gastrointestinal stromal tumours is mediated by primary cilia. Gastric Cancer 2020; 23: 64-72.
Vidal MT, Lourenço SV, Soares FA, et al. The sonic hedgehog signaling pathway contributes to the development of salivary gland neoplasms regardless of perineural infiltration. Tumour Biol 2016; 37: 9587-9601.
Andersson MK, Afshari MK, Andrén Y, et al. Targeting the oncogenic transcriptional regulator MYB in adenoid cystic carcinoma by inhibition of IGF1R/AKT signaling. J Natl Cancer Inst 2017; 109: djx017.
Sugimura H, Mori H, Nagura K, et al. Fluorescence in situ hybridization analysis with a tissue microarray: ‘FISH and chips’ analysis of pathology archives. Pathol Int 2010; 60: 543-550.
Shinmura K, Goto M, Suzuki M, et al. Reduced expression of MUTYH with suppressive activity against mutations caused by 8-hydroxyguanine is a novel predictor of a poor prognosis in human gastric cancer. J Pathol 2011; 225: 414-423.
Takaku Y, Suzuki H, Kawasaki H, et al. A modified ‘NanoSuit®’ preserves wet samples in high vacuum: direct observations on cells and tissues in field-emission scanning electron microscopy. R Soc Open Sci 2017; 4: 160887.
Kawasaki H, Itoh T, Takaku Y, et al. The NanoSuit method: a novel histological approach for examining paraffin sections in a nondestructive manner by correlative light and electron microscopy. Lab Invest 2020; 100: 161-173.
Shinmura K, Kawasaki H, Baba S, et al. Utility of scanning electron microscopy elemental analysis using the ‘NanoSuit’ correlative light and electron microscopy method in the diagnosis of lanthanum phosphate deposition in the esophagogastroduodenal mucosa. Diagnostics (Basel) 2019; 10: 1.
Sharpe HJ, Pau G, Dijkgraaf GJ, et al. Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma. Cancer Cell 2015; 27: 327-341.
Lo CH, Lin IH, Yang TT, et al. Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation. J Cell Biol 2019; 218: 3489-3505.
Shinmura K, Kato H, Kawanishi Y, et al. Defective repair capacity of variant proteins of the DNA glycosylase NTHL1 for 5-hydroxyuracil, an oxidation product of cytosine. Free Radic Biol Med 2019; 131: 264-273.
Sipos É, Komoly S, Ács P. Quantitative comparison of primary cilia marker expression and length in the mouse brain. J Mol Neurosci 2018; 64: 397-409.
Nagao T, Sato E, Inoue R, et al. Immunohistochemical analysis of salivary gland tumors: application for surgical pathology practice. Acta Histochem Cytochem 2012; 45: 269-282.
Yasar B, Linton K, Slater C, et al. Primary cilia are increased in number and demonstrate structural abnormalities in human cancer. J Clin Pathol 2017; 70: 571-574.
Triantafyllou A, Mikkelsen LH, Gnepp DR, et al. Salivary myoepithelial cells: an addendum. Ultrastruct Pathol 2018; 42: 465-476.
Shinmura K, Iwaizumi M, Igarashi H, et al. Induction of centrosome amplification and chromosome instability in p53-deficient lung cancer cells exposed to benzo[a]pyrene diol epoxide (B[a]PDE). J Pathol 2008; 216: 365-374.
Buslei R, Rushing EJ, Giangaspero F, et al. Craniopharyngioma. In WHO Classification of Tumours of the Central Nervous System (Revised 4th edn), Louis DN, Ohgaki H, Wiestler OD, et al. (eds). IARC: Lyon, 2016; 324-328.
Carr RA, Taibjee SM, Sanders DSM. Basaloid skin tumours: basal cell carcinoma. Curr Diagn Pathol 2007; 13: 252-272.
Otsuka A, Dreier J, Cheng PF, et al. Hedgehog pathway inhibitors promote adaptive immune responses in basal cell carcinoma. Clin Cancer Res 2015; 21: 1289-1297.
Peer E, Tesanovic S, Aberger F. Next-generation Hedgehog/GLI pathway inhibitors for cancer therapy. Cancers (Basel) 2019; 11: 538.
Takahashi M, Tomizawa K, Sato K, et al. A novel tau-tubulin kinase from bovine brain. FEBS Lett 1995; 372: 59-64.
Čajánek L, Nigg EA. Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole. Proc Natl Acad Sci U S A 2014; 111: E2841-E2850.
Huang N, Zhang D, Li F, et al. M-Phase Phosphoprotein 9 regulates ciliogenesis by modulating CP110-CEP97 complex localization at the mother centriole. Nat Commun 2018; 9: 4511.
Bernatik O, Pejskova P, Vyslouzil D, et al. Phosphorylation of multiple proteins involved in ciliogenesis by Tau Tubulin kinase 2. Mol Biol Cell 2020; 31: 1032-1046.
Bowie E, Norris R, Anderson KV, et al. Spinocerebellar ataxia type 11-associated alleles of Ttbk2 dominantly interfere with ciliogenesis and cilium stability. PLoS Genet 2018; 14: e1007844.
Avasthi P, Marshall WF. Stages of ciliogenesis and regulation of ciliary length. Differentiation 2012; 83: S30-S42.
Lu H, Toh MT, Narasimhan V, et al. A function for the Joubert syndrome protein Arl13b in ciliary membrane extension and ciliary length regulation. Dev Biol 2015; 397: 225-236.