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FCH domain only 1 (FCHo1), a potential new biomarker for lung cancer

Abstract

Lung carcinoma is the main reason for cancer-associated deaths in the world. In a previous study, FCH domain only 1 (FCHo1) which is managed by protein kinase B (AKT), was shown to be activated in lung cancer. FCHo1 knockdown has previously been shown to cause cell death in lung cancer. However, the specific roles of FCHo1 in lung carcinoma remain elusive. Herein, we propose that FCHo1’s intracellular mechanism targets the G1 to S phase transition, following the M phase. We demonstrated that F-BAR and mu homology domains exist separately in human lung tissues and that one truncated form is not detected in patients with lung cancer. Furthermore, quantitative global proteome analysis of FCHo1 indicated that the inhibition of G1/S phase transition and FCHo1 RNAi led to the death of cells in the G1/S phase. Noninvasive viral aerosol-mediated delivery of FCHo1 shRNA suppressed cancer progression in mice with non-small-cell lung cancer (NSCLC), suggesting that the delivery of FCHo1 shRNA could be a meaningful therapeutic strategy in lung cancer. Additional studies are needed to make clear the detailed mechanism of action of FCHo1.

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Fig. 1: Truncated FCHo1 has a different distribution in lung cancer patients.
Fig. 2: Quantitative global proteome analysis in FCHo1-overexpressing A549 cells.
Fig. 3: FCHo1 siRNA leads to cell death in A549 lung cancer cells during the cell cycle.
Fig. 4: FCHo1 shRNA inhibits lung tumorigenesis in K-RasLA1 mice.

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Acknowledgements

This work was supported by BK21 PLUS Program for Creative Veterinary Science Research. This work was financially supported by a research fund from Chungnam National University (grant to JP).

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SP, JP, and MHC designed the entire study and wrote the manuscript. SP and AYL performed experiments including immunoprecipitations, live cell imaging, RTCA proliferation assays, lentivirus production, and DNA construct cloning, and contributed equally to the data interpretation and the writing and preparation of the manuscript. AYL, SK, and SHH performed the in vivo experiment. KCC and JHJ performed the proteomics analysis and contributed to data interpretation and manuscript preparation. JP, KPK, and MHC jointly supervised the study. All authors discussed the results and reviewed the manuscript.

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Correspondence to Kwang Pyo Kim, Jongsun Park or Myung-Haing Cho.

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Park, S., Lee, A.Y., Cho, KC. et al. FCH domain only 1 (FCHo1), a potential new biomarker for lung cancer. Cancer Gene Ther 29, 901–907 (2022). https://doi.org/10.1038/s41417-021-00376-8

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