Sorting nexin 10 acts as a tumor suppressor in tumorigenesis and progression of colorectal cancer through regulating chaperone mediated autophagy degradation of p21<sup>Cip1/WAF1</sup>.
Overall, our data will inform future studies to elucidate the mechanisms of p21WAF1/CIP1 transcriptional regulation, and the functional roles of p21WAF1/CIP1 in breast cancer tumorigenesis.
The current data indicated that SOX6 is a novel target of miR-155 and that miR-155 enhances liver cell tumorigenesis at least in part through the novel miR-155/SOX6/p21waf1/cip1 axis.
Thus, our results suggest that KLF4 may function as a tumor suppressor in the skin and that the deregulated expression of KLF4 in the context of p21(Waf1/Cip1) and cyclin D1 expression may be involved in skin tumorigenesis.
Our results suggest that hypermethylation does not contribute to P21(CIP1) and P27(KIP1) silencing in gastric cancer, and that the role of these genes in the gastric tumorigenesis pathways should be studied further in the Pará state population.
Taken together, we conclude that p21(Cip1) functions as a tumor suppressor in cervical carcinogenesis and that p21(Cip1) inactivation by HPV-16 E7 partially contributes to the contribution of E7 to cervical carcinogenesis.
Further, tumorigenesis in Dcn(-/-) mice was associated with disruption of intestinal maturation, including decreased cell differentiation and increased proliferation, which were linked to the downregulation of p21(WAF1/cip1), p27(kip1), intestinal trefoil factor and E-cadherin and to the upregulation of beta-catenin signaling.
We focused on an inferred core network with CDKN1A (p21(WAF1/CIP1)) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM).
Artepillin C appears to prevent colon cancer through the induction of cell-cycle arrest by stimulating the expression of Cip1/p21 and to be a useful chemopreventing factor in colon carcinogenesis.
Abolition of p21(Cip1/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis.
We have found that the cyclin-dependent kinase inhibitor p21(WAF1/cip1) plays a major role in regulating several aspects of mucosal homeostasis and the response to dietary and pharmacologic modulators of tumorigenesis; that disruption of lineages of differentiation of intestinal epithelial cells are intimately involved in tumor formation; and that important pathways that contribute to normal homeostasis and cancer development may be coordinately regulated by mitochondrial function, with the mitochondrial membrane potential playing a key role.
The most intriguing features of the study were: (a) the significant increase in frequency of this polymorphism not only in patients with oral SCCs (P = 0.038), but also in patients with premalignant lesions (P = 0.038), compared with normal controls; and (b) the significantly higher frequency of p21(Waf1/Cip1) variants (codon 149) in oral premalignant lesions (10 of 11 cases) and SCCs (11 of 11 cases) with wild-type p53 (P = 0.045) than in lesions with p53 mutations, suggesting that this polymorphism affects the p53 pathway and may play a vital role in oral tumorigenesis.
Analysis of p21(waf1/cip1) expression in relation to p53 gene and protein status revealed its induction by p53-dependent as well as independent pathways in esophageal tumorigenesis.
Because cell cycle disruption appears crucial for tumorigenesis, we analyzed the immunohistochemical expression patterns of the prototype cyclin-dependent kinase inhibitor p21 WAF1/CIP1 and the proliferation marker Ki67 in the early stages of colorectal tumorigenesis.
We observed a marked decrease in CDC2 and CDK2 kinase activity associated with a corresponding decrease in the amount of CDC2 but not CDK2 protein; a decreased growth potential of Adp21WAF1/CIP1-infected cells demonstrated by diminished [3H]thymidine incorporation, increased cell doubling time and G1-arrested cell cycle; an association between Adp21WAF1/CIP1-infected cells and inhibition of aneuploid cell accumulation; and an alteration of the malignant phenotype of cells was evidenced by the loss of anchorage-independent growth in soft agar and the failure to induce tumorigenesis in both peripheral and intracerebral xenograft models, including the prevention of tumor formation Adp21WAF1/CIP1 infection 2 days post tumor cell implantation.Adp21WAF1/CIP1.
These results indicate that reduced expression of p21 Cip1 mRNA is critical for growth activity and malignant potential of human colorectal carcinoma, and that the decrease in p21 Cip1 mRNA level is due to p53 gene mutation as well as other mechanisms during human colorectal carcinogenesis.