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Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion.

ABSTRACT: Fat mass and obesity-associated protein (FTO), an RNA N⁶-methyladenosine (m⁶A) demethylase, plays oncogenic roles in various cancers, presenting an opportunity for the development of effective targeted therapeutics. Here, we report two potent small-molecule FTO inhibitors that exhibit strong anti-tumor effects in multiple types of cancers. We show that genetic depletion and pharmacological inhibition of FTO dramatically attenuate leukemia stem/initiating cell self-renewal and reprogram immune response by suppressing expression of immune checkpoint genes, especially LILRB4. FTO inhibition sensitizes leukemia cells to T cell cytotoxicity and overcomes hypomethylating agent-induced immune evasion. Our study demonstrates that FTO plays critical roles in cancer stem cell self-renewal and immune evasion and highlights the broad potential of targeting FTO for cancer therapy.

SUBMITTER: Su R

PROVIDER: S-EPMC7363590 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Targeting FTO suppresses cancer stem cell maintance and immune evasion

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Targeting FTO suppresses cancer stem cell maintance and immune evasion

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Targeting Arginine Methylation Suppresses Cancer Stem Cell Maintenance and Elicits cGAS-mediated anti-Cancer Immunity

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