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Cancer-cell intrinsic electrical activity drives small-cell lung cancer progression

ABSTRACT: Cancer-cell intrinsic electrical activity drives small-cell lung cancer progression

PROVIDER: PRJNA1126122 | ENA |

REPOSITORIES: ENA

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Cancer-cell intrinsic electrical activity drives small-cell lung cancer progression

Project description:Elevated or ectopic expression of neuronal receptors and ion channels promotes tumor progression in many cancer types; neuroendocrine (NE) transformation of various adenocarcinomas has also been associated with increased aggressiveness. Whether the defining neuronal feature, namely electrical excitability, exists in cancer cells and whether this impacts cancer progression remains mostly unexplored. Small cell lung cancer (SCLC) is an archetypical example of highly aggressive NE cancers and is comprised of two major distinct subtypes of cancer cells: NE cells and non-NE cells. Here, we show that the NE cells are excitable, like neurons, while non-NE cells cannot fire action potentials, like astrocytes and other non-excitable cells. Action potential firing in NE cells directly promotes SCLC malignancy; however, the high ATP demand of electrical activity also leads to an unusual dependency on oxidative phosphorylation (OXPHOS) in NE cells. This finding contrasts with most cancer cells reported in the literature, which are non-excitable and heavily rely on aerobic glycolysis. Additionally, we find that non-NE cells metabolically support NE cells to supply their high ATP demand, promoting their excitability and malignancy, a process akin to the astrocyte-neuron metabolite shuttle. Lastly, we observe drastic changes in the innervation landscape during SCLC progression, which coincide with increased intratumoral heterogeneity (ITH) and elevated neuronal protein expression in SCLC cells, suggesting an induction of a tumor autonomous vicious cycle driven by cancer cell-intrinsic electrical activity, which confers long-term tumorigenic capability and metastatic potential.

2024-11-07 | GSE270281 | GEO

Tumor cell-intrinsic ATP6V0A1 drives immunosuppressive reprogramming in colorectal cancer

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Wireless Electrical-Molecular Quantum Signalling for Cancer Cell Induced Death

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The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFNb pathway Phospho

Project description:Phosphoproteomics show that the tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFNb pathway

2021-01-15 | MSV000086706 | MassIVE

The tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFNb pathway Proteome

Project description:Proteome analysis reveals that the tumor suppressor kinase DAPK3 drives tumor-intrinsic immunity through the STING-IFNb pathway Proteome

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Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance

Project description:Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance

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Tumor cell-intrinsic Piezo2 drives radioresistance by impairing CD8+ T cell stemness maintenance

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| PRJNA990673 | ENA

Intrinsic epigenetic state of primary osteosarcoma drives metastasis.

Project description:Intrinsic epigenetic state of primary osteosarcoma drives metastasis.

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Trichuris muris infection drives cell-intrinsic IL4R alpha independent large intestinal RELMα+ macrophages.

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A comprehensive PDX gastric cancer collection captures cancer cell intrinsic transcriptional MSI traits.

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