Animal experiments show that α2-ADR agonists attenuate the injury-induced Müller cell dedifferentiation by a mechanism that involves activation and regulation of extracellular signal-regulated kinase (ERK) 1/2 leading to transactivation of epidermal growth factor receptors (EGFRs).
According to this view, antibodies or kinase inhibitors targeting EGFR-HER2 effectively retard some solid tumors because they arrest mutation-enriched TACs and possibly inhibit their dedifferentiation.
Epidermal growth factor receptor mutation analysis revealed the same mutation (p.delL747-T751) in both areas, suggesting that the malignant rhabdoid phenotype represents a dedifferentiation phenomenon of the adenocarcinoma.
The therapeutic role of EGFR inhibitors in thyroid malignancies is still controversial even though the full activation of EGF signaling has recently been proposed as involved in the dedifferentiation of human thyroid cancers.
Here, we demonstrate that combined loss of p16(INK4a) and p19(ARF), but not of p53, p16(INK4a), or p19(ARF), enables astrocyte dedifferentiation in response to EGFR activation.
A trend toward increased expression of EGF-R and TGFalpha protein with dedifferentiation and a similar trend in the growth fraction suggest a role in tumor progression.