Myoferlin Is a Yet Unknown Interactor of the Mitochondrial Dynamics' Machinery in Pancreas Cancer Cells

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Jun 25

PMID 32575867

Citations 8

Authors

Sandy Anania

Raphael Peiffer

Gilles Rademaker

Alexandre Hego

Marc Thiry

Louise Deldicque

Marc Francaux

Naima Maloujahmoum

Ferman Agirman

Akeila Bellahcene

Vincent Castronovo

Olivier Peulen

Affiliations

Soon will be listed here.

Abstract

Pancreas ductal adenocarcinoma is one of the deadliest cancers where surgery remains the main survival factor. Mitochondria were described to be involved in tumor aggressiveness in several cancer types including pancreas cancer. We have previously reported that myoferlin controls mitochondrial structure and function, and demonstrated that myoferlin depletion disturbs the mitochondrial dynamics culminating in a mitochondrial fission. In order to unravel the mechanism underlying this observation, we explored the myoferlin localization in pancreatic cancer cells and showed a colocalization with the mitochondrial dynamic machinery element: mitofusin. This colocalization was confirmed in several pancreas cancer cell lines and in normal cell lines as well. Moreover, in pancreas cancer cell lines, it appeared that myoferlin interacted with mitofusin. These discoveries open-up new research avenues aiming at modulating mitofusin function in pancreas cancer.

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References

Leung C, Utokaparch S, Sharma A, Yu C, Abraham T, Borchers C . Proteomic identification of dysferlin-interacting protein complexes in human vascular endothelium. Biochem Biophys Res Commun. 2011; 415(2):263-9. DOI: 10.1016/j.bbrc.2011.10.031. View

Filadi R, Greotti E, Pizzo P . Highlighting the endoplasmic reticulum-mitochondria connection: Focus on Mitofusin 2. Pharmacol Res. 2018; 128:42-51. DOI: 10.1016/j.phrs.2018.01.003. View

Cao Y, Meng S, Chen Y, Feng J, Gu D, Yu B . MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion. Nature. 2017; 542(7641):372-376. PMC: 5319402. DOI: 10.1038/nature21077. View

Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P . Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proc Natl Acad Sci U S A. 2015; 112(17):E2174-81. PMC: 4418914. DOI: 10.1073/pnas.1504880112. View

Chen H, Detmer S, Ewald A, Griffin E, Fraser S, Chan D . Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol. 2003; 160(2):189-200. PMC: 2172648. DOI: 10.1083/jcb.200211046. View

Kumar S, Pan C, Shah N, Wheeler S, Hoyt K, Hempel N . Activation of Mitofusin2 by Smad2-RIN1 Complex during Mitochondrial Fusion. Mol Cell. 2016; 62(4):520-31. PMC: 4877164. DOI: 10.1016/j.molcel.2016.04.010. View

Yu M, Nguyen N, Huang Y, Lin D, Fujimoto T, Molkentine J . Mitochondrial fusion exploits a therapeutic vulnerability of pancreatic cancer. JCI Insight. 2019; 5. PMC: 6777817. DOI: 10.1172/jci.insight.126915. View

Doghman-Bouguerra M, Lalli E . ER-mitochondria interactions: Both strength and weakness within cancer cells. Biochim Biophys Acta Mol Cell Res. 2019; 1866(4):650-662. DOI: 10.1016/j.bbamcr.2019.01.009. View

Redpath G, Sophocleous R, Turnbull L, Whitchurch C, Cooper S . Ferlins Show Tissue-Specific Expression and Segregate as Plasma Membrane/Late Endosomal or Trans-Golgi/Recycling Ferlins. Traffic. 2015; 17(3):245-66. DOI: 10.1111/tra.12370. View

10.

Wang W, Liu X, Liu L, Lou W, Jin D, Yang P . iTRAQ-based quantitative proteomics reveals myoferlin as a novel prognostic predictor in pancreatic adenocarcinoma. J Proteomics. 2013; 91:453-65. DOI: 10.1016/j.jprot.2013.06.032. View

11.

Dong Y, Kang H, Liu H, Wang J, Guo Q, Song C . Myoferlin, a Membrane Protein with Emerging Oncogenic Roles. Biomed Res Int. 2019; 2019:7365913. PMC: 6885792. DOI: 10.1155/2019/7365913. View

12.

Friedman J, Lackner L, West M, Dibenedetto J, Nunnari J, Voeltz G . ER tubules mark sites of mitochondrial division. Science. 2011; 334(6054):358-62. PMC: 3366560. DOI: 10.1126/science.1207385. View

13.

Chan D . Mitochondrial Dynamics and Its Involvement in Disease. Annu Rev Pathol. 2019; 15:235-259. DOI: 10.1146/annurev-pathmechdis-012419-032711. View

14.

Porcelli L, Iacobazzi R, Di Fonte R, Serrati S, Intini A, Solimando A . CAFs and TGF-β Signaling Activation by Mast Cells Contribute to Resistance to Gemcitabine/Nabpaclitaxel in Pancreatic Cancer. Cancers (Basel). 2019; 11(3). PMC: 6468868. DOI: 10.3390/cancers11030330. View

15.

Rademaker G, Costanza B, Anania S, Agirman F, Maloujahmoum N, Di Valentin E . Myoferlin Contributes to the Metastatic Phenotype of Pancreatic Cancer Cells by Enhancing Their Migratory Capacity through the Control of Oxidative Phosphorylation. Cancers (Basel). 2019; 11(6). PMC: 6628295. DOI: 10.3390/cancers11060853. View

16.

Viale A, Pettazzoni P, Lyssiotis C, Ying H, Sanchez N, Marchesini M . Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014; 514(7524):628-32. PMC: 4376130. DOI: 10.1038/nature13611. View

17.

Martins de Brito O, Scorrano L . Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature. 2008; 456(7222):605-10. DOI: 10.1038/nature07534. View

18.

Barnhouse V, Weist J, Shukla V, Ghadiali S, Kniss D, Leight J . Myoferlin regulates epithelial cancer cell plasticity and migration through autocrine TGF-β1 signaling. Oncotarget. 2018; 9(27):19209-19222. PMC: 5922389. DOI: 10.18632/oncotarget.24971. View

19.

Chen H, Chan D . Mitochondrial Dynamics in Regulating the Unique Phenotypes of Cancer and Stem Cells. Cell Metab. 2017; 26(1):39-48. PMC: 5539982. DOI: 10.1016/j.cmet.2017.05.016. View

20.

Cowan D, Yao R, Thedsanamoorthy J, Zurakowski D, Del Nido P, McCully J . Transit and integration of extracellular mitochondria in human heart cells. Sci Rep. 2017; 7(1):17450. PMC: 5727261. DOI: 10.1038/s41598-017-17813-0. View