{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:19:07Z","timestamp":1789510747199,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,22]],"date-time":"2019-12-22T00:00:00Z","timestamp":1576972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aims of this study were to investigate the role of nerve growth factor on perineural invasion in oral and salivary gland tumour cell lines and whether there is an involvement of PI3K\/Akt pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Four cell lines were investigated: HSG and TYS (salivary gland tumours), SAS\u2010H1 (oral squamous cell carcinoma) and HaCaT (human skin keratinocyte). Initially, Boyden chamber assay was done to examine the effect of different concentration of nerve growth factor on cell migration. Western blot\/ immunofluorescence techniques were used to investigate the phosphorylation status of the Akt pathway within the cells in response to nerve growth factor. The effect of this growth factor and the addition of an Akt inhibitor on cell morphology and migration were also examined using scatter\/scratch assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nerve growth factor triggered the PI3K\/Akt pathway in oral and salivary tumour cells and induced oral and salivary tumour cell scattering and migration. Inhibitor assays confirmed that oral and salivary gland tumour cell scattering and migration is Akt dependent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nerve growth factor can stimulate scattering and migration in cells derived from oral and salivary gland tumours, thereby potentially enhancing perineural invasion. Phosphorylated Akt controls cancer cell migration and scattering. Blocking the Akt pathway may inhibit cell migration and therefore perineural invasion and metastasis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12979","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T12:12:33Z","timestamp":1575029553000},"page":"227-234","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Nerve growth factor\u2010induced migration in oral and salivary gland tumour cells utilises the PI3K\/Akt signalling pathway: Is there a link to perineural invasion?"],"prefix":"10.1111","volume":"49","author":[{"given":"Huda","family":"Alkhadar","sequence":"first","affiliation":[{"name":"Unit of Cell and Molecular Biology Dundee Dental School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaelina","family":"Macluskey","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Medicine and Pathology Dundee Dental School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"White","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery, Medicine and Pathology Dundee Dental School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8035-6012","authenticated-orcid":false,"given":"Ian","family":"Ellis","sequence":"additional","affiliation":[{"name":"Unit of Cell and Molecular Biology Dundee Dental School University of Dundee Dundee UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034518756297"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rcl.2016.08.006"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2009.07.001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81683-9"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568009043332853"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/08977190903578678"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.8.2419"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2006.00037.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers3010510"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.02.004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2010.01.006"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.12133"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0123"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2005.12.011"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1746-1596-4-18"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24732"},{"issue":"3","key":"e_1_2_8_18_1","first-page":"496","article-title":"An adenoid squamous carcinoma\u2010forming cell line established from an oral keratinizing squamous cell carcinoma expressing carcinoembryonic antigen","volume":"124","author":"Yanagawa T","year":"1986","journal-title":"Am J Pathol"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01209653"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19810801)48:3<745::AID-CNCR2820480314>3.0.CO;2-7"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.3.761"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2010.04.003"},{"key":"e_1_2_8_23_1","first-page":"1","article-title":"The motogenic effect of EGF and TGF\u2010\u03b1 on the migration of tumor cells from the oral region: a role of epithelial\u2010to\u2010mesenchymal transition in cancer and a route for translation into the clinic","volume":"2","author":"Islam M","year":"2017","journal-title":"Transl Res Oral Oncol"},{"key":"e_1_2_8_24_1","first-page":"23","article-title":"Wound\u2010healing assay","volume":"294","author":"Rodriguez LG","year":"2005","journal-title":"Methods Mol. 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