Neurotrophin Pathway Receptors NGFR and TrkA Control Perineural Invasion, Metastasis, and Pain in Oral Cancer.
Carcinoma, Squamous Cell
/ genetics
Head and Neck Neoplasms
Humans
Mouth Neoplasms
/ genetics
Neoplasm Invasiveness
/ genetics
Neoplasm Recurrence, Local
Neoplastic Processes
Nerve Growth Factors
Nerve Tissue Proteins
Pain
Receptor Protein-Tyrosine Kinases
Receptor, Nerve Growth Factor
Receptor, trkA
Receptors, Nerve Growth Factor
/ genetics
Squamous Cell Carcinoma of Head and Neck
cancer pain
metastasis
neurotrophin
oral cancer
perineural invasion
Journal
Advanced biology
ISSN: 2701-0198
Titre abrégé: Adv Biol (Weinh)
Pays: Germany
ID NLM: 101775319
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
14
07
2022
received:
06
07
2022
pubmed:
5
8
2022
medline:
14
9
2022
entrez:
4
8
2022
Statut:
ppublish
Résumé
Oral squamous cell carcinoma (OSCC) patients suffer from poor survival due to metastasis or locoregional recurrence, processes that are both facilitated by perineural invasion (PNI). OSCC has higher rates of PNI than other cancer subtypes, with PNI present in 80% of tumors. Despite the impact of PNI on oral cancer prognosis and pain, little is known about the genes that drive PNI, which in turn drive pain, invasion, and metastasis. In this study, clinical data, preclinical, and in vitro models are leveraged to elucidate the role of neurotrophins in OSCC metastasis, PNI, and pain. The expression data in OSCC patients with metastasis, PNI, or pain demonstrate dysregulation of neurotrophin genes. TrkA and nerve growth factor receptor (NGFR) are focused, two receptors that are activated by NGF, a neurotrophin expressed at high levels in OSCC. It is demonstrated that targeted knockdown of these two receptors inhibits proliferation and invasion in an in vitro and preclinical model of OSCC, and metastasis, PNI, and pain. It is further determined that TrkA knockdown alone inhibits thermal hyperalgesia, whereas NGFR knockdown alone inhibits mechanical allodynia. Collectively the results highlight the ability of OSCC to co-opt different components of the neurotrophin pathway in metastasis, PNI, and pain.
Identifiants
pubmed: 35925599
doi: 10.1002/adbi.202200190
pmc: PMC9533666
mid: NIHMS1828809
doi:
Substances chimiques
NGFR protein, human
0
NTRK1 protein, human
0
Nerve Growth Factors
0
Nerve Tissue Proteins
0
Receptor, Nerve Growth Factor
0
Receptors, Nerve Growth Factor
0
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
Receptor, trkA
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2200190Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE031395
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047063
Pays : United States
Organisme : NIDCR NIH HHS
ID : L30 DE031145
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047820
Pays : United States
Organisme : NIDCR NIH HHS
ID : K23 DE030250
Pays : United States
Informations de copyright
© 2022 The Authors. Advanced Biology published by Wiley-VCH GmbH.
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