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

Cancer Gene Therapy volume 29, pages 901–907 (2022)Cite this article

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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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References

  1. Henne WM, Boucrot E, Meinecke M, Evergren E, Vallis Y, Mittal R, et al. FCHo proteins are nucleators of clathrin-mediated endocytosis. Science 2010;328:1281–4.

    Article  CAS  Google Scholar 

  2. Henne WM, Kent HM, Ford MGJ, Hegde BG, Daumke O, Butler PJG, et al. Structure and analysis of FCHo2F-BAR domain: a dimerizing and membrane recruitment module that effects membrane curvature. Structure 2007;15:839–52.

    Article  CAS  Google Scholar 

  3. Lyszkiewicz M, Zietara N, Frey L, Pannicke U, Stern M, Liu Y, et al. Human FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells. Nat Commun. 2020;11:1031.

    Article  CAS  Google Scholar 

  4. Umasankar PK, Sanker S, Thieman JR, Chakraborty S, Wendland B, Tsang M, et al. Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning. Nat Cell Biol. 2012;14:488–501.

    Article  CAS  Google Scholar 

  5. Park S, Hong Y, Lee S, Lee AY, Tran Q, Lee H. et al. FCHO1560-571 peptide, a PKB kinase motif, inhibits tumor progression. Biochem Biophys Res Commun. 2020;528:478–484.

    Article  CAS  Google Scholar 

  6. Aviner R, Shenoy A, Elroy-Stein O, Geiger T. Uncovering hidden layers of cell cycle regulation through integrative multi-omic analysis. PLoS Genet. 2015;11(10):e1005554.

  7. Vakifahmetoglu H, Olsson M, Zhivotovsky B. Death through a tragedy: mitotic catastrophe. Cell Death Differ. 2008;15:1153–62.

    Article  CAS  Google Scholar 

  8. Chieffi P, Aurora B. A new promising therapeutic target in cancer. Intractable Rare Dis Res. 2018;7:141–4.

    Article  Google Scholar 

  9. McDonald NA, Takizawa Y, Feoktistova A, Xu P, Ohi MD, Vander Kooi CW, et al. The tubulation activity of a fission yeast F-BAR protein is dispensable for its function in cytokinesis. Cell Rep. 2016;14:534–46.

    Article  CAS  Google Scholar 

  10. Finkel T, Hwang PM. The Krebs cycle meets the cell cycle: mitochondria and the G(1)-S transition. Proc Natl Acad Sci USA. 2009;106:11825–6.

    Article  CAS  Google Scholar 

  11. Sugiyama M, Sakaue-Sawano A, Iimura T, Fukami K, Kitaguchi T, Kawakami K, et al. Illuminating cell-cycle progression in the developing zebrafish embryo. Proc Natl Acad Sci USA. 2009;106:20812–7.

    Article  CAS  Google Scholar 

  12. Wragg JW, Roos L, Vucenovic D, Cvetesic N, Lenhard B, Mueller F. Zebrafish embryonic tissue differentiation is marked by concurrent cell cycle dynamic and gene promoter regulatory changes. 2020;48(15):8374-8392.

  13. Bavetsias V, Linardopoulos S. Aurora kinase inhibitors: current status and outlook. Front Oncol. 2015;5:278.

  14. Hong SH, Chang SH, Cho KC, Kim S, Park S, Lee AY, et al. Endoplasmic reticulum–Golgi intermediate compartment protein 3 knockdown suppresses lung cancer through endoplasmic reticulum stress-induced autophagy. Oncotarget 2016;7:65335–47.

    Article  Google Scholar 

  15. Wisniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat Methods. 2009;6:359–62.

    Article  CAS  Google Scholar 

  16. Hoerth P, Miller CA, Preckel T, Wenz C. Efficient fractionation and improved protein identification by peptide OFFGEL electrophoresis. Mol Cell Proteom. 2006;5:1968–74.

    Article  CAS  Google Scholar 

  17. Searle BC. Scaffold: a bioinformatic tool for validating MS/MS-based proteomic studies. Proteomics 2010;10:1265–9.

    Article  CAS  Google Scholar 

  18. Chang S-H, Hong S-H, Jiang H-L, Minai-Tehrani A, Yu K-N, Lee J-H, et al. GOLGA2/GM130, cis-Golgi matrix protein, is a novel target of anticancer gene therapy. Mol Ther. 2012;20:2052–63.

    Article  CAS  Google Scholar 

  19. Hong S-H, Minai-Tehrani A, Chang S-H, Jiang H-L, Lee S, Lee A-Y, et al. Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis. PLoS ONE. 2013;8:e77121.

    Article  CAS  Google Scholar 

  20. Hong S-H, Park S-J, Lee S, Cho CS, Cho M-H. Aerosol gene delivery using viral vectors and cationic carriers for in vivo lung cancer therapy. Expert Opin Drug Deliv. 2015;12:977–91.

    Article  CAS  Google Scholar 

  21. Islam MA, Shin J-Y, Yun C-H, Cho C-S, Seo HW, Chae C, et al. The effect of RNAi silencing of p62 using an osmotic polysorbitol transporter on autophagy and tumorigenesis in lungs of K-ras(LA1) mice. Biomaterials 2014;35:1584–96.

    Article  CAS  Google Scholar 

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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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Author notes

  1. Sungjin Park

    Present address: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, USA

  2. Kyung-Cho Cho

    Present address: Medical Research Center, Seoul National University, Seoul, Republic of Korea

  3. Seong-Ho Hong

    Present address: Bio Medicine Laboratory, CKD Research Institute, Yongin, Republic of Korea

  4. These authors contributed equally: Sungjin Park, Ah Young Lee, Kyung-Cho Cho.

Authors and Affiliations

  1. Laboratory of Toxicology, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea

    Sungjin Park, Ah Young Lee, Seong-Ho Hong, Sanghwa Kim & Myung-Haing Cho

  2. Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin, Republic of Korea

    Kyung-Cho Cho, Jae Hun Jung & Kwang Pyo Kim

  3. Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul, Republic of Korea

    Kyung-Cho Cho, Jae Hun Jung & Kwang Pyo Kim

  4. Department of Pharmacology and Medical Science, Metabolic Syndrome and Cell Signaling Laboratory, Institute for Cancer Research, College of Medicine, Chungnam National University, Daejeon, Republic of Korea

    Jongsun Park

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Contributions

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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