Isoform switch of CD47 provokes macrophage-mediated pyroptosis in ovarian cancer DOI Creative Commons
Zixiang Wang, Lei Yang, Siyuan Yang

и другие.

Опубликована: Апрель 18, 2025

Abstract Cancer cells expressing CD47 escape macrophage phagocytosis by binding to the SIRPα ligand expressed on macrophages. targeted therapy offers a promising approach cancer treatment. Here we report that two major isoforms of differ in ovarian and normal tissues. The truncated isoform lacking exon 9 10 (CD47-S) was exclusively tissues, whereas full-length (CD47-L) predominantly Interestingly, CD47-S unable locate at cell surface bind with as CD47-L did, thereby inactivated “don’t-eat-me” signal. Mechanistic investigations revealed splicing factor HNRNPA1 promoted switch from through skipping. We further developed antisense oligonucleotides (ASOs) effectively switched . Importantly, ASOs treatment evoked macrophage-mediated antitumor immune response, triggered pyroptosis cells. Moreover, CD47-targeting significantly reduced tumor growth patient-derived xenograft. Together, ASO-mediated has emerged strategy improve responses against tumors.

Язык: Английский

Isoform switch of CD47 provokes macrophage-mediated pyroptosis in ovarian cancer DOI Creative Commons
Zixiang Wang, Lei Yang, Siyuan Yang

и другие.

Опубликована: Апрель 18, 2025

Abstract Cancer cells expressing CD47 escape macrophage phagocytosis by binding to the SIRPα ligand expressed on macrophages. targeted therapy offers a promising approach cancer treatment. Here we report that two major isoforms of differ in ovarian and normal tissues. The truncated isoform lacking exon 9 10 (CD47-S) was exclusively tissues, whereas full-length (CD47-L) predominantly Interestingly, CD47-S unable locate at cell surface bind with as CD47-L did, thereby inactivated “don’t-eat-me” signal. Mechanistic investigations revealed splicing factor HNRNPA1 promoted switch from through skipping. We further developed antisense oligonucleotides (ASOs) effectively switched . Importantly, ASOs treatment evoked macrophage-mediated antitumor immune response, triggered pyroptosis cells. Moreover, CD47-targeting significantly reduced tumor growth patient-derived xenograft. Together, ASO-mediated has emerged strategy improve responses against tumors.

Язык: Английский

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