Producción CyT
Congreso
Autoría
Santiago Madera
;
BULIAN, VALENTINA CELINE
;
Sharon S. Merin
;
María F. Mercogliano
;
Roxana Schillaci
;
Rosalia I. Cordo Russo
Fecha
2023
Editorial y Lugar de Edición
AACR
ISSN
0008-5472
Resumen
Información suministrada por el agente en
SIGEVA
Hyaluronan (HA), a linear glycosaminoglycan, is a prominent component of the extracellular matrixwithin the tumor microenvironment. Through its interaction with the CD44 receptor, a type I transmembrane glycoprotein, HA promotes oncogenic signals, activates migration and metastasis, and induces resistance to antineoplastic agents. A novel aspect of CD44 biology was the discovery of its ability to migrate to the nuclear compartment and to activate the transcription of genes. Overexpression of Er...
Hyaluronan (HA), a linear glycosaminoglycan, is a prominent component of the extracellular matrixwithin the tumor microenvironment. Through its interaction with the CD44 receptor, a type I transmembrane glycoprotein, HA promotes oncogenic signals, activates migration and metastasis, and induces resistance to antineoplastic agents. A novel aspect of CD44 biology was the discovery of its ability to migrate to the nuclear compartment and to activate the transcription of genes. Overexpression of ErbB-2, a member of ErbB family of receptor tyrosine kinases, occurs in 15-20% of breast cancers (BC) and is considered a major oncogenic driver. Despite clinical efficiency of ErbB-2-targeted therapies (e.g. trastuzumab), resistance is a major issue. While ErbB-2 is mainly a cell membrane-bound receptor, it can migrate to the nucleus (NErbB-2) where it acts as a transcription factor or coactivator.Accumulation of HA is associated with poor prognosis and promotes resistance to anti-ErbB-2 agent trastuzumab (TZ) in BC. Although crosstalk between HA/CD44 and ErbB-2 pathways has been reported, how their molecular interactions mediate TZ resistance remains unknown.Here, we explored the ability of HA to modulate CD44 and ErbB-2 nuclear localization as well as therole of HA in proliferation and migration of BC cells resistant to anti-ErbB-2 agents.
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Palabras Clave
4MUTrastuzumab (TZ)Tumor progressionNuclear localization