In addition, in primary myofibroblast-like cells that were obtained from a patient with pulmonary fibrosis, treatment with CsA and an HIF-1α inhibitor (HIFi) decreased the expression levels of α-smooth muscle actin and fibronectin, which indicated that CsA and HIFi promote dedifferentiation of myofibroblasts.
Here, we report that hypoxia-inducible factor (HIF-1α) and cancer-associated fibroblasts (CAFs)-secreted TGF-β2 converge to activate the expression of hedgehog transcription factor GLI2 in CSCs, resulting in increased stemness/dedifferentiation and intrinsic resistance to chemotherapy.
High expression of heparanase is significantly associated with dedifferentiation and lymph node metastasis in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA and via HIF1a to HB-EGF and bFGF.
These data are consistent with the concept, that "aberrant" CAIX staining - meaning absent or weak staining in a cancer expected to have a high level CAIX expression such as clear cell RCC or detectable CAIX expression in tumors that are typically CAIX negative such as papillary and chromophobe RCC - reflects biologic tumor dedifferentiation.
Moreover, p53 serves as a barrier for dedifferentiation and reprogramming by constraining the cells to a somatic state and preventing their conversion to SCs.
Some of the main genetic changes of differentiated thyroid carcinomas, such as mutations in BRAF and RAS genes, as well as changes in CTNNB1, PIK3CA, TP53, AXIN1, PTEN or APC genes leading to the dedifferentiation of the tumors, are described.
This last observation led us to investigate the role of BRAF(V600E) and the MEK-ERK pathway in thyroid dedifferentiation, particularly in Na(+)/I(-) symporter (NIS) impairment, as this thyroid-specific plasma membrane glycoprotein mediates active transport of I(-) into the thyroid follicular cells.
In this study, we try to clarify the changes of dedifferentiation and cell proliferative activity and their relationship in small HCCs (less than 3.0 cm in diameter) and try to learn the mechanism of these changes by analysing the expressions and genetic changes of proliferation-related genes p53 and beta-catenin.
One case that experienced 17p loss was classified as favourable histology at diagnosis, but exhibited diffuse anaplasia at recurrence and had a homozygous TP53 deletion.
In addition, TBB reduced the expression of type II collagen and stimulated the accumulation of β‑catenin, phenotypic markers of chondrocyte differentiation and dedifferentiation, respectively.
Overexpression of p53 correlated with increased proliferation and dedifferentiation, as demonstrated by immunohistochemistry and in situ hybridization using histone H3 and cytokeratin-specific probes.
Co-expression of MDM2/CDK4 (p=0.001) and TP53 accumulation (p=0.017) related to dedifferentiation but not to recurrence or death, both in WDLPS and DDLPS.
These data support the key role of TP53 loss in the development of anaplasia in WT, and support its significant clinical impact in patients with residual anaplastic tumor following surgery.
There was no statistically significant association between histological type, tumor stage, pleural invasion, tumor size (P > 0.05 for all) and E-cadherin/beta-catenin expression.Reduced E-cadherin or beta-catenin negative expression relates to dedifferentiation and progression of NSCLC.
Activation of canonical wingless-type MMTV integration site family (Wnt) signaling in mature adipocytes increases beta-catenin levels and leads to cell dedifferentiation and insulin resistance.
The inactivation of wild-type TP53 is an earlier event before dedifferentiation of TUB to mixed-type UGC, but is less frequent and a later event in a subset of mixed-type UGC deriving from SIG..
This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways.