Muscleblind-like 1 Suppresses Breast Cancer Metastatic Colonization and Stabilizes Metastasis Suppressor Transcripts

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2016 Feb 18

PMID 26883358

Citations 41

Authors

Lisa Fish

Nora Pencheva

Hani Goodarzi

Hien Tran

Mitsukuni Yoshida

Sohail F Tavazoie

Affiliations

Soon will be listed here.

Abstract

Post-transcriptional deregulation is a defining feature of metastatic cancer. While many microRNAs have been implicated as regulators of metastatic progression, less is known about the roles and mechanisms of RNA-binding proteins in this process. We identified muscleblind-like 1 (MBNL1), a gene implicated in myotonic dystrophy, as a robust suppressor of multiorgan breast cancer metastasis. MBNL1 binds the 3' untranslated regions (UTRs) of DBNL (drebrin-like protein) and TACC1 (transforming acidic coiled-coil containing protein 1)-two genes that we implicate as metastasis suppressors. By enhancing the stability of these genes' transcripts, MBNL1 suppresses cell invasiveness. Consistent with these findings, elevated MBNL1 expression in human breast tumors is associated with reduced metastatic relapse likelihood. Our findings delineate a post-transcriptional network that governs breast cancer metastasis through RNA-binding protein-mediated transcript stabilization.

Citing Articles

NE-MTOC Formation in Skeletal Muscle Is Mbnl2-Dependent and Occurs in a Sequential and Gradual Manner.

Das P, Becker R, Vergarajauregui S, Engel F Cells. 2025; 14(4).

PMID: 39996710 PMC: 11853192. DOI: 10.3390/cells14040237.

Functions of the Muscleblind-like protein family and their role in disease.

Zhou H, Xu J, Pan L Cell Commun Signal. 2025; 23(1):97.

PMID: 39966885 PMC: 11837677. DOI: 10.1186/s12964-025-02102-5.

Involvement of circRNA Regulators MBNL1 and QKI in the Progression of Esophageal Squamous Cell Carcinoma.

Wang H, Zhou X, Zhang Q, Wu J, Hou J, Xu X Cancer Control. 2024; 31:10732748241257142.

PMID: 38769028 PMC: 11107321. DOI: 10.1177/10732748241257142.

MBNL1 Regulates Programmed Postnatal Switching Between Regenerative and Differentiated Cardiac States.

Bailey L, Bugg D, Reichardt I, Ortac C, Nagle A, Gunaje J Circulation. 2024; 149(23):1812-1829.

PMID: 38426339 PMC: 11147738. DOI: 10.1161/CIRCULATIONAHA.123.066860.

Functional requirement of alternative splicing in epithelial-mesenchymal transition of pancreatic circulating tumor.

Xiao L, Sun H, Cheng R, Yang R, Jin X, Xu Z Mol Ther Nucleic Acids. 2024; 35(1):102129.

PMID: 38370981 PMC: 10869908. DOI: 10.1016/j.omtn.2024.102129.

References

Kessels M, Drubin D . Association of mouse actin-binding protein 1 (mAbp1/SH3P7), an Src kinase target, with dynamic regions of the cortical actin cytoskeleton in response to Rac1 activation. Mol Biol Cell. 2000; 11(1):393-412. PMC: 14781. DOI: 10.1091/mbc.11.1.393. View

Miller J, Urbinati C, Stenberg M, Byrne B, Thornton C, Swanson M . Recruitment of human muscleblind proteins to (CUG)(n) expansions associated with myotonic dystrophy. EMBO J. 2000; 19(17):4439-48. PMC: 302046. DOI: 10.1093/emboj/19.17.4439. View

Liquori C, Ricker K, Moseley M, Jacobsen J, Kress W, Naylor S . Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science. 2001; 293(5531):864-7. DOI: 10.1126/science.1062125. View

Lauffart B, Howell S, Tasch J, Cowell J, Still I . Interaction of the transforming acidic coiled-coil 1 (TACC1) protein with ch-TOG and GAS41/NuBI1 suggests multiple TACC1-containing protein complexes in human cells. Biochem J. 2002; 363(Pt 1):195-200. PMC: 1222467. DOI: 10.1042/0264-6021:3630195. View

Conte N, Charafe-Jauffret E, Delaval B, Adelaide J, Ginestier C, Geneix J . Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. Oncogene. 2002; 21(36):5619-30. DOI: 10.1038/sj.onc.1205658. View

Kanadia R, Urbinati C, Crusselle V, Luo D, Lee Y, Harrison J . Developmental expression of mouse muscleblind genes Mbnl1, Mbnl2 and Mbnl3. Gene Expr Patterns. 2003; 3(4):459-62. DOI: 10.1016/s1567-133x(03)00064-4. View

Conte N, Delaval B, Ginestier C, Ferrand A, Isnardon D, Larroque C . TACC1-chTOG-Aurora A protein complex in breast cancer. Oncogene. 2003; 22(50):8102-16. DOI: 10.1038/sj.onc.1206972. View

Kanadia R, Johnstone K, Mankodi A, Lungu C, Thornton C, Esson D . A muscleblind knockout model for myotonic dystrophy. Science. 2003; 302(5652):1978-80. DOI: 10.1126/science.1088583. View

Ho T, Charlet-B N, Poulos M, Singh G, Swanson M, Cooper T . Muscleblind proteins regulate alternative splicing. EMBO J. 2004; 23(15):3103-12. PMC: 514918. DOI: 10.1038/sj.emboj.7600300. View

10.

Brook J, McCurrach M, Harley H, Buckler A, Church D, Aburatani H . Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992; 68(4):799-808. DOI: 10.1016/0092-8674(92)90154-5. View

11.

Begemann G, Paricio N, Artero R, Kiss I, Perez-Alonso M, Mlodzik M . muscleblind, a gene required for photoreceptor differentiation in Drosophila, encodes novel nuclear Cys3His-type zinc-finger-containing proteins. Development. 1997; 124(21):4321-31. DOI: 10.1242/dev.124.21.4321. View

12.

Artero R, Prokop A, Paricio N, Begemann G, Pueyo I, Mlodzik M . The muscleblind gene participates in the organization of Z-bands and epidermal attachments of Drosophila muscles and is regulated by Dmef2. Dev Biol. 1998; 195(2):131-43. DOI: 10.1006/dbio.1997.8833. View

13.

Larbolette O, Wollscheid B, Schweikert J, Nielsen P, Wienands J . SH3P7 is a cytoskeleton adapter protein and is coupled to signal transduction from lymphocyte antigen receptors. Mol Cell Biol. 1999; 19(2):1539-46. PMC: 116082. DOI: 10.1128/MCB.19.2.1539. View

14.

Minn A, Gupta G, Siegel P, Bos P, Shu W, Giri D . Genes that mediate breast cancer metastasis to lung. Nature. 2005; 436(7050):518-24. PMC: 1283098. DOI: 10.1038/nature03799. View

15.

Pascual M, Vicente M, Monferrer L, Artero R . The Muscleblind family of proteins: an emerging class of regulators of developmentally programmed alternative splicing. Differentiation. 2006; 74(2-3):65-80. DOI: 10.1111/j.1432-0436.2006.00060.x. View

16.

Connert S, Wienand S, Thiel C, Krikunova M, Glyvuk N, Tsytsyura Y . SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired vesicle transport. EMBO J. 2006; 25(8):1611-22. PMC: 1440832. DOI: 10.1038/sj.emboj.7601053. View

17.

Lin X, Miller J, Mankodi A, Kanadia R, Yuan Y, Moxley R . Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Hum Mol Genet. 2006; 15(13):2087-97. DOI: 10.1093/hmg/ddl132. View

18.

Linder S . The matrix corroded: podosomes and invadopodia in extracellular matrix degradation. Trends Cell Biol. 2007; 17(3):107-17. DOI: 10.1016/j.tcb.2007.01.002. View

19.

Gupta G, Nguyen D, Chiang A, Bos P, Kim J, Nadal C . Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature. 2007; 446(7137):765-70. DOI: 10.1038/nature05760. View

20.

Keene J . RNA regulons: coordination of post-transcriptional events. Nat Rev Genet. 2007; 8(7):533-43. DOI: 10.1038/nrg2111. View