Nucleostemin upregulation and STAT3 activation as early events in oral epithelial dysplasia progression to squamous cell carcinoma

Autor: Yi-Shing L Cheng, Madeleine Crawford, Robert Yl Tsai, Xiaoqin Liu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
STAT3 Transcription Factor
Original article
immunohistochemistry
(IHC)
Cancer Research
Epithelial dysplasia
Prognosis prediction
head and neck squamous cell carcinoma
(HNSCC)
Oral premalignant lesion
medicine.disease_cause
Cancer prevention
Rats
Sprague-Dawley
Downregulation and upregulation
GTP-Binding Proteins
Sprague-Dawley
(SD)
medicine
Animals
Humans
Basal cell
RC254-282
Leukoplakia
Risk assessment
Stat3 activation
oral premalignant lesion
(OPL)
phospho-STAT3
(p-STAT3)
Squamous Cell Carcinoma of Head and Neck
business.industry
Nuclear Proteins
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Short-Tagged Sequence
(STS)
medicine.disease
Epithelium
Rats
Up-Regulation
4-nitroquinoline-1-oxide
(4NQO)
stomatognathic diseases
medicine.anatomical_structure
Dysplasia
nucleostemin
(NS)
Disease Progression
Cancer research
oral squamous cell carcinoma
(OSCC)
Mouth Neoplasms
Oral epithelial dysplasia
Carcinogenesis
business
Precancerous Conditions
Zdroj: Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 12, Pp 1289-1299 (2021)
Neoplasia (New York, N.Y.)
ISSN: 1476-5586
Popis: Highlight • Nucleostemin expression differentiates early and late oral carcinogenic lesions. • p-STAT3, a nucleostemin target, increases during oral precancer progression. • Nucleolar signals of nucleostemin discern static and progressive dysplasia. • Nucleostemin may be used to assess the cancer risk of low-grade dysplasia.
Most low-grade oral epithelial dysplasia remains static or regress, but a significant minority of them (4–11%) advances to oral squamous cell carcinoma (OSCC) within a few years. To monitor the progression of epithelial dysplasia for early cancer detection, we investigated the expression profiles of nucleostemin (NS) and phospho-STAT3 (p-STAT3) in rodent and human samples of dysplasia and OSCCs. In a 4NQO-induced rat oral carcinogenesis model, the number and distribution of NS and p-STAT3-positive cells increased in hyperplastic, dysplastic, and neoplastic lesions compared to normal epithelium. In human samples, the NS signal significantly increased in high-grade dysplasia and poorly differentiated OSCC, whereas p-STAT3 was more ubiquitously expressed than NS and showed increased intensity in high-grade dysplasia and both well and poorly differentiated OSCC. Analyses of human dysplastic samples with longitudinally followed outcomes revealed that cells with prominent nucleolar NS signals were more abundant in low-grade dysplasia that advanced to OSCC in 2 or 3 years than those remaining static for 7–14 years. These results suggest that NS upregulation and STAT3 activation are early events in the progression of low-grade dysplasia to OSCC.
Databáze: OpenAIRE
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