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Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination.

ABSTRACT: While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease.

SUBMITTER: Chou CW

PROVIDER: S-EPMC10582093 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination.

Chou Chih-Wei CW Hung Chia-Nung CN Chiu Cheryl Hsiang-Ling CH Tan Xi X Chen Meizhen M Chen Chien-Chin CC Saeed Moawiz M Hsu Che-Wei CW Liss Michael A MA Wang Chiou-Miin CM Lai Zhao Z Alvarez Nathaniel N Osmulski Pawel A PA Gaczynska Maria E ME Lin Li-Ling LL Ortega Veronica V Kirma Nameer B NB Xu Kexin K Liu Zhijie Z Kumar Addanki P AP Taverna Josephine A JA Velagaleti Gopalrao V N GVN Chen Chun-Liang CL Zhang Zhao Z Huang Tim Hui-Ming TH

Nature communications 20231017 1

While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the ent ...[more]

PMID: 37848444

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Project description:Mammalian Myc proteins are important determinants of cell proliferation as well as the undifferentiated state of stem cells and their activity is frequently deregulated in cancer. Based mainly on conservation in the C-terminal DNA-binding and dimerization domain, Myc-like proteins have been reported in many simpler organisms within and outside the Metazoa but they have not been found in fungi or plants. Several important signature motifs defining mammalian Myc proteins are found in the N-terminal domain but the extent to which these are found in the Myc-like proteins from simpler organisms is not well established. The extent of N-terminal signature sequence conservation would give important insights about the evolution of Myc proteins and their current function in mammalian physiology and disease. In a systematic study of Myc-like proteins we show that N-terminal signature motifs are not readily detectable in individual Myc-like proteins from invertebrates but that weak similarities to Myc boxes 1 and 2 can be found in the N-termini of the simplest Metazoa as well as the unicellular choanoflagellate, Monosiga brevicollis, using multiple protein alignments. Phylogenetic support for the connections of these proteins to established Myc proteins is however poor. We show that the pattern of predicted protein disorder along the length of Myc proteins can be used as a complementary approach to making dendrograms of Myc proteins that aids the classification of Myc proteins. This suggests that the pattern of disorder within Myc proteins is more conserved through evolution than their amino acid sequence. In the disorder-based dendrograms the Myc-like proteins from simpler organisms, including M. brevicollis, are connected to established Myc proteins with a higher degree of certainty. Our results suggest that protein disorder based dendrograms may be of general significance for studying distant relationships between proteins, such as transcription factors, that have high levels of intrinsic disorder.

Dataset Information

Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination.

Publications

Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination.

Similar Datasets

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