The potential role of human endogenous retrovirus K in glioblastoma
Parvinder Hothi, Charles Cobbs
Parvinder Hothi, Charles Cobbs
Published July 3, 2023
Citation Information: J Clin Invest. 2023;133(13):e170885. https://doi.org/10.1172/JCI170885.
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The potential role of human endogenous retrovirus K in glioblastoma

Abstract

The most active human endogenous retrovirus K (HERV-K) subtype, HML-2, has been implicated as a driver of oncogenesis in several cancers. However, the presence and function of HML-2 in malignant gliomas has remained unclear. In this issue of the JCI, Shah and colleagues demonstrate HML-2 overexpression in glioblastoma (GBM) and its role in maintaining the cancer stem cell phenotype. Given that stem-like cells are considered responsible for GBM heterogeneity and treatment resistance, targeting the stem cell niche may reduce tumor recurrence and improve clinical outcomes. The findings provide a foundation for future studies to determine whether antiretroviral and/or immunotherapy approaches targeting HML-2 could be used as therapeutics for GBM.

Authors

Parvinder Hothi, Charles Cobbs

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Figure 1

HML-2 drives the GBM cancer stem cell phenotype and promotes GBM pathogenesis.

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HML-2 drives the GBM cancer stem cell phenotype and promotes GBM pathoge...
GBM stem-like cells are thought to derive from subependymal zone glial precursor stem cells. Mutations in these glial precursor cells contribute to transformation and development of GBM stem-like cells, which often express OCT4, SOX2, etc. These cells promote further GBM cell proliferation and invasion and resistance to chemotherapy. Shah and colleagues showed that HML-2 drives the GBM cancer stem cell phenotype and, thus, promotes GBM pathogenesis (6).