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Co-culture CRISPR screens reveal ATG9A as a regulator to macrophage-mediated cytotoxicity in cancer

ABSTRACT: This study investigates the role of cancer cell surface proteins in modulating the response of cancer cells to macrophage-induced cytotoxicity. Utilizing two targeted CRISPR screens using OVCAR-8 cell line and a targeted CRISPR library for cancer cell surface proteins, ATG9A was identified as a key regulator. ATG9A KO increased the sensitivity of cancer cells to macrophage-induced cytotoxicity. Subsequent surface and whole-cell mass spectrometry analysis elucidated the underlying mechanisms; ATG9A KO in cancer cells not only enhances macrophage infiltration and activation but also plays a crucial role in the plasma membrane repair following macrophage co-culture. These findings reveal novel targets for enhancing macrophage-mediated cytotoxicity in cancer, offering additional avenues for therapeutic intervention.

INSTRUMENT(S): timsTOF Pro 2

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Abhilash Barpanda

LAB HEAD: Arun Wiita

PROVIDER: PXD053872 | Pride | 2025-04-29

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	2023-04-10-decoys-uniprot_hum_proteome.fasta	Fasta
	230901_AK_oa1_Slot2-27_1_183.mzML	Mzml
	230901_AK_oa2_Slot2-28_1_184.mzML	Mzml
	230901_AK_oa3_Slot2-29_1_185.mzML	Mzml
	230901_AK_og1_Slot2-30_1_188.mzML	Mzml

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Co-culture CRISPR screens reveal ATG9A as a regulator to macrophage-mediated cytotoxicity in cancer

Project description:This study investigates the role of cancer cell surface proteins in modulating the response of cancer cells to macrophage-induced cytotoxicity. Utilizing two targeted CRISPR screens using OVCAR-8 cell line and a targeted CRISPR library for cancer cell surface proteins, ATG9A was identified as a key regulator. ATG9A KO increased the sensitivity of cancer cells to macrophage-induced cytotoxicity. Subsequent RNA sequencing and other analysis elucidated the underlying mechanisms; ATG9A KO in cancer cells not only enhances inflammatory cytokines production but also plays a crucial role in the plasma membrane repair following macrophage co-culture. These findings reveal novel targets for enhancing macrophage-mediated cytotoxicity in cancer, offering additional avenues for therapeutic intervention.

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Co-culture CRISPR screens reveal ATG9A as a regulator to macrophage-mediated cytotoxicity in cancer

Project description:Co-culture CRISPR screens reveal ATG9A as a regulator to macrophage-mediated cytotoxicity in cancer

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Human Serum, Following Absorption of Fish Cartilage Hydrolysate, Promotes Dermal Fibroblast Healing through Anti-Inflammatory and Immunomodulatory Proteins

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