Loss of FAM83H promotes cell migration and invasion in cutaneous squamous cell carcinoma via impaired keratin distribution.
Animals
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Proliferation
/ genetics
DNA-Binding Proteins
/ metabolism
Epidermis
/ metabolism
Female
Gene Expression
Gene Knockdown Techniques
Humans
Keratinocytes
Keratins
/ metabolism
Mice
Mice, Inbred BALB C
Neoplasm Grading
Neoplasm Invasiveness
/ genetics
Neoplasm Metastasis
Neoplasm Transplantation
Proteins
/ genetics
RNA, Messenger
/ metabolism
Skin Neoplasms
/ genetics
Transcription Factors
/ metabolism
FAM83H
Squamous cell carcinoma
TRIM29, keratin distribution
Journal
Journal of dermatological science
ISSN: 1873-569X
Titre abrégé: J Dermatol Sci
Pays: Netherlands
ID NLM: 9011485
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
24
05
2021
revised:
13
09
2021
accepted:
23
09
2021
pubmed:
19
10
2021
medline:
25
2
2022
entrez:
18
10
2021
Statut:
ppublish
Résumé
FAM83H is essential for amelogenesis, but recent reports implicate that FAM83H is involved in the tumorigenesis. We previously clarified that TRIM29 binds to FAM83H to regulate keratin distribution and squamous cell migration. However, little is known about FAM83H in normal/malignant skin keratinocytes. To investigate the expression of FAM83H in cutaneous squamous cell carcinoma (SCC) and its physiological function. Immunohistochemical analysis and RT-PCR of human SCC tissues were performed. Next, we examined the effect of FAM83H knockdown/overexpression in SCC cell lines using cell proliferation, migration, and invasion assay. To investigate the molecular mechanism, immunoprecipitation of FAM83H was examined. Further, Immunofluorescence staining was performed. Finally, we examined the correlation between the expressions of FAM83H and the keratin distribution. FAM83H expression was lower in SCC lesions than in normal epidermis and correlated with differentiation grade. The mRNA expression levels of FAM83H in SCC tumors were also lower than in normal epidermis. The knockdown of FAM83H enhanced SCC cell migration and invasion, whereas the overexpression of FAM83H led to decreases in both. Furthermore, the knockdown of FAM83H enhanced the cancer cell metastasis in vivo. FAM83H formed a complex with TRIM29 and keratins. The knockdown of FAM83H altered keratin distribution and solubility. Clinically, the loss of FAM83H correlates with an altered keratin distribution. Our findings reveal a critical function for FAM83H in regulating keratin distribution, as well as in the migration/invasion of cutaneous SCC, suggesting that FAM83H could be a crucial molecule in the tumorigenesis of cutaneous SCC.
Sections du résumé
BACKGROUNDS
BACKGROUND
FAM83H is essential for amelogenesis, but recent reports implicate that FAM83H is involved in the tumorigenesis. We previously clarified that TRIM29 binds to FAM83H to regulate keratin distribution and squamous cell migration. However, little is known about FAM83H in normal/malignant skin keratinocytes.
OBJECTIVE
OBJECTIVE
To investigate the expression of FAM83H in cutaneous squamous cell carcinoma (SCC) and its physiological function.
METHODS
METHODS
Immunohistochemical analysis and RT-PCR of human SCC tissues were performed. Next, we examined the effect of FAM83H knockdown/overexpression in SCC cell lines using cell proliferation, migration, and invasion assay. To investigate the molecular mechanism, immunoprecipitation of FAM83H was examined. Further, Immunofluorescence staining was performed. Finally, we examined the correlation between the expressions of FAM83H and the keratin distribution.
RESULTS
RESULTS
FAM83H expression was lower in SCC lesions than in normal epidermis and correlated with differentiation grade. The mRNA expression levels of FAM83H in SCC tumors were also lower than in normal epidermis. The knockdown of FAM83H enhanced SCC cell migration and invasion, whereas the overexpression of FAM83H led to decreases in both. Furthermore, the knockdown of FAM83H enhanced the cancer cell metastasis in vivo. FAM83H formed a complex with TRIM29 and keratins. The knockdown of FAM83H altered keratin distribution and solubility. Clinically, the loss of FAM83H correlates with an altered keratin distribution.
CONCLUSION
CONCLUSIONS
Our findings reveal a critical function for FAM83H in regulating keratin distribution, as well as in the migration/invasion of cutaneous SCC, suggesting that FAM83H could be a crucial molecule in the tumorigenesis of cutaneous SCC.
Identifiants
pubmed: 34657752
pii: S0923-1811(21)00224-3
doi: 10.1016/j.jdermsci.2021.09.007
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
FAM83H protein, human
0
Proteins
0
RNA, Messenger
0
TRIM29 protein, human
0
Transcription Factors
0
Keratins
68238-35-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
112-121Informations de copyright
Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors have no conflicts of interest to declare.