ABSTRACT
Mesenchymal to epithelial transition factor (MET) gene alterations involve in the proliferation, invasion, and metastasis of non-small cell lung cancer. MET-tyrosine kinase inhibitors (TKIs) have been approved to treat non-small cell lung cancer with MET alterations, and resistance to these TKIs is inevitable. Molecular mechanisms of resistance to MET-TKIs are completely unclear. The review focused on potential mechanisms of MET-TKIs resistance and therapeutics strategies to delay and prevent resistance. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , ErbB Receptors/genetics , Drug Resistance, Neoplasm/genetics , Protein Kinase Inhibitors/therapeutic use , Epithelial-Mesenchymal Transition , MutationABSTRACT
The generation of induced pluripotent stem cells through somatic cell reprogramming requires a global reorganization of cellular functions. This reorganization occurs in a multi-phased manner and involves a gradual revision of both the epigenome and transcriptome. Recent studies have shown that the large-scale transcriptional changes observed during reprogramming also apply to long non-coding RNAs (lncRNAs), a type of traditionally neglected RNA species that are increasingly viewed as critical regulators of cellular function. Deeper understanding of lncRNAs in reprogramming may not only help to improve this process but also have implications for studying cell plasticity in other contexts, such as development, aging, and cancer. In this review, we summarize the current progress made in profiling and analyzing the role of lncRNAs in various phases of somatic cell reprogramming, with emphasis on the re-establishment of the pluripotency gene network and X chromosome reactivation.
ABSTRACT
Objective To investigate the association between expression of the epithelial?to?mesenchymal transition(EMT)biomarkers and the malignant progression of gastric cancer in primary tumors and metastases and their possible correlation with progression of gastric cancer(GC). Methods The EMT biomarkers including E?cadherin,β?catenin,N?cadherin,Snail and TGF?β1 were detected by immunohistochemical method for 145 cases of gastric cancer(GC),25 cases of abnormal hyperplasia,13 cases of intestinal metaplasia,42 cases of lymph node metastasis and 40 cases of normal gastric mucosa tissues. Results Positive rates of TGF?β1,Snail,E?cadherin,β?catenin and N?cadherin were 73.5%,65.5%, 14.5%,53.1%and 35.9%,respectively,in gastric cancer tissues and 100%,100%,0%,27.5%and 2.5%,respectively,in normal gastric tissues, with a significant difference between the two groups(P<0.05). The decreased expression of E?cadherin andβ?catenin and the increased expression of TGF?β1 were related to the depth of invasion of gastric cancer(P<0.05). The expression of E?cadherin was correlated positively with the expres?sion ofβ?catenin,but negatively with the expression of TGF?β1. Whereas,the expression of N?cadherin was correlated positively with the expression of TGF?β1(P<0.05). The expression of E?cadherin andβ?catenin in lymph node metastasis was significantly higher than that in gastric cancer tis?sues,while the expression of TGF?β1 was lower than in gastric cancer tissues(P<0.05). Conclusion The increased expression of TGF?β1 and Snail and the decreased expression of E?cadherin,β?catenin,and N?cadherin are involved in the processes of invasion and metastasis of GC. The transformation of E?cadherin to N?cadherin and the expression of TGF?β1 may play an important role in the development of GC. In lymph node me?tastasis,the phenomenon of mesenchymal?to?epithelial transition(MET)occurs.
ABSTRACT
Mesenchymal to epithelial transition (MET), whereby mesenchymal cells become more epithelial like in phenotype, was observed to occur during normal development and in cancers. Numerous investigations have been conducted on MET in carcino-mas. In addition, accumulating evidence also suggests the critical function of MET in sarcomas. Integrated analyses reveal that MET may be an important biological and clinical process in sarcomas, and transcription factors such as Slug may also perform central func-tions in epithelial differentiation in several sarcomas such as leiomyo-sarcoma and synovial sarcoma. Given the scarcity of investiga-tions and evidence, several important issues about MET, such as its molecular markers, signaling mechanisms, micro RNA regulations, and clinical significance, need to be clarified. In this article, we review several important questions about MET in sarcomas, including molecular markers, signaling mechanisms, regulation by miRNAs, and therapeutic implications.