Investigating the anti-proliferative functions of co-opted HERV-derived proteins in cancer

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Abstract
Human endogenous retroviruses (HERVs) are remains of ancient viral infections, with some retaining functional genes like the HERV-T envelope protein, hsaHTenv. Prior studies have identified monocarboxylate transporter 1 (MCT1), a primary key in cancer metabolism, as the receptor for the ancestral form of this protein (ancHTenv). In humans, hsaHTenv may act as a natural MCT1 blocker, suggesting potential tumor-suppressive roles. This thesis characterizes the expression and function of HERV-derived proteins in cancer cells, focusing on the effects of hsaHTenv in K562 leukemia cells. Using qPCR and Western blotting, we profiled HERV expression and analyzed how it responds to metabolic modulation. Functional assays, including CellTiter-Glo assay, were used to assess the impact of hsaHTenv overexpression on cell proliferation and viability.We further investigated whether hsaHTenv-mediated suppression of MCT1 mimics the effects of pharmacological inhibition using AR-C155858. The results demonstrate that hsaHTenv disrupts cancer cell growth and metabolic balance, supporting its potential as a biological alternative to MCT1 targeting drug. Overall, this study suggests that HERV-derived proteins like hsaHTenv may serve as natural regulators of cancer metabolism and highlights their promise as novel tools in anti-cancer strategies.
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2025
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