RESUMEN
Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.
Asunto(s)
Cadherinas/genética , Carcinogénesis/genética , Transición Epitelial-Mesenquimal/genética , Genes de Cambio , Animales , Antineoplásicos/aislamiento & purificación , Antineoplásicos/uso terapéutico , Descubrimiento de Drogas/métodos , Descubrimiento de Drogas/tendencias , Regulación Neoplásica de la Expresión Génica , Genes de Cambio/genética , Humanos , Terapia Molecular Dirigida/métodos , Terapia Molecular Dirigida/normas , Terapia Molecular Dirigida/tendencias , Familia de Multigenes/genética , Transducción de Señal/genéticaRESUMEN
Signal Transducer and Activator of Transcription (STAT) pathway is connected upstream with Janus kinases (JAK) family protein and capable of integrating inputs from different signaling pathways. Each family member plays unique functions in signal transduction and crucial in mediating cellular responses to different kind of cytokines. STAT family members notably STAT3 and STAT5 have been involved in cancer progression whereas STAT1 plays opposite role by suppressing tumor growth. Persistent STAT3/5 activation is known to promote chronic inflammation, which increases susceptibility of healthy cells to carcinogenesis. Here, we review the role of STATs in cancers and inflammation while discussing current therapeutic implications in different cancers and test models, especially the delivery of STAT3/5 targeting siRNA using nanoparticulate delivery system.
