Author:
Doucet-O’Hare Tara T.,Rosenblum Jared S.,Shah Ashish H.,Gilbert Mark R.,Zhuang Zhengping
Abstract
Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell properties to cells. We recently demonstrated that the most recently incorporated HERV element (HERV-K HML-2) has been associated with the pathogenesis of the embryonal atypical teratoid rhabdoid tumor (AT/RT), shifting our understanding of embryonal tumor development. HML-2 expression is vital for proper human development and its expression is suppressed via methylation or chromatin remodeling as cells differentiate. We previously found that dysfunctional chromatin remodeling due to loss of SMARCB1 expression induces HML-2 envelope (env) expression, impairing cellular differentiation and migration, and facilitating tumor growth in AT/RT. Epigenetic dysregulation in other embryonal tumors with concomitant expression of stem-cell markers may facilitate HML-2 expression. Future studies could utilize HML-2 as potential diagnostic criteria, use its expression as a treatment biomarker, and investigate the efficacy of therapies targeting cells with high HML-2 expression.
Cited by
3 articles.
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