A Possible Role for the Wnt~1 Pathway in Oral Carcinogenesisreview
Аннотация: Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease for all cancers. Proteins involved in intercellular adhesion, such as E-cadherin and catenin, probably play an important role in metastatic processes and cellular differentiation. While E-cadherin and beta-catenin expression has been extensively studied in many forms of human cancers, less is known about the role of the Wingless-Type-1 (WNT-1 ) pathway in human tumors. A large body of genetic and biochemical evidence has identified beta-catenin as a key downstream component of the WNT signaling pathway, and recent studies of colorectal tumors have shown a functional link among beta-catenin, adenomatous polyposis coli gene product (APC), and other components of the WNT-1 pathway. WNT-1 pathway signaling is thought to be mediated via interactions between beta-catenin and members of the LEF-1/TCF family of transcription factors. The WNT signal stabilizes beta-catenin protein and promotes its accumulation in the cytoplasm and nucleus. In the nucleus, beta-catenin associates with TCF to form a functional transcription factor which mediates the transactivation of target genes involved in the promotion of tumor progression, invasion, and metastasis, such as C-Myc, cyclin DI, c-jun, fra-1, and u-PAR. There is a strong correlation between the ability of the WNT-1 gene to induce beta-catenin accumulation and its transforming potential in vivo, suggesting that the WNT-1 gene activates an intracellular signaling pathway that can induce the morphological transformation of cells. For these reasons, data obtained from the study of the WNT-1 pathway could be important in our understanding of the mechanisms of epithelial tumors, in general, and probably also of oral squamous cell carcinoma, in particular.
Год издания: 2001
Авторы: Lorenzo Lo Muzio
Издательство: SAGE Publishing
Источник: Critical Reviews in Oral Biology & Medicine
Ключевые слова: Wnt/β-catenin signaling in development and cancer, Cancer-related gene regulation, Kruppel-like factors research
Другие ссылки: Critical Reviews in Oral Biology & Medicine (PDF)
Critical Reviews in Oral Biology & Medicine (HTML)
PubMed (HTML)
Critical Reviews in Oral Biology & Medicine (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 12
Выпуск: 2
Страницы: 152–165