PMID- 30408026 OWN - NLM STAT- MEDLINE DCOM- 20190617 LR - 20240404 IS - 1545-7885 (Electronic) IS - 1544-9173 (Print) IS - 1544-9173 (Linking) VI - 16 IP - 11 DP - 2018 Nov TI - TRIM59 promotes breast cancer motility by suppressing p62-selective autophagic degradation of PDCD10. PG - e3000051 LID - 10.1371/journal.pbio.3000051 [doi] LID - e3000051 AB - Cancer cells adopt various modes of migration during metastasis. How the ubiquitination machinery contributes to cancer cell motility remains underexplored. Here, we report that tripartite motif (TRIM) 59 is frequently up-regulated in metastatic breast cancer, which is correlated with advanced clinical stages and reduced survival among breast cancer patients. TRIM59 knockdown (KD) promoted apoptosis and inhibited tumor growth, while TRIM59 overexpression led to the opposite effects. Importantly, we uncovered TRIM59 as a key regulator of cell contractility and adhesion to control the plasticity of metastatic tumor cells. At the molecular level, we identified programmed cell death protein 10 (PDCD10) as a target of TRIM59. TRIM59 stabilized PDCD10 by suppressing RING finger and transmembrane domain-containing protein 1 (RNFT1)-induced lysine 63 (K63) ubiquitination and subsequent phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa (p62)-selective autophagic degradation. TRIM59 promoted PDCD10-mediated suppression of Ras homolog family member A (RhoA)-Rho-associated coiled-coil kinase (ROCK) 1 signaling to control the transition between amoeboid and mesenchymal invasiveness. PDCD10 overexpression or administration of a ROCK inhibitor reversed TRIM59 loss-induced contractile phenotypes, thereby accelerating cell migration, invasion, and tumor formation. These findings establish the rationale for targeting deregulated TRIM59/PDCD10 to treat breast cancer. FAU - Tan, Peng AU - Tan P AD - Department of Medical Oncology and Biomedical Research Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. AD - Center for Translational Cancer Research, Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, Texas, United States of America. FAU - Ye, Youqiong AU - Ye Y AD - Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, United States of America. FAU - He, Lian AU - He L AUID- ORCID: 0000-0002-8842-235X AD - Center for Translational Cancer Research, Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, Texas, United States of America. FAU - Xie, Jiansheng AU - Xie J AD - Department of Medical Oncology and Biomedical Research Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Jing, Ji AU - Jing J AUID- ORCID: 0000-0003-1004-8377 AD - Center for Translational Cancer Research, Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, Texas, United States of America. FAU - Ma, Guolin AU - Ma G AUID- ORCID: 0000-0001-5460-3446 AD - Center for Translational Cancer Research, Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, Texas, United States of America. FAU - Pan, Hongming AU - Pan H AD - Department of Medical Oncology and Biomedical Research Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Han, Leng AU - Han L AUID- ORCID: 0000-0002-7380-2640 AD - Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston McGovern Medical School, Houston, Texas, United States of America. FAU - Han, Weidong AU - Han W AD - Department of Medical Oncology and Biomedical Research Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China. FAU - Zhou, Yubin AU - Zhou Y AUID- ORCID: 0000-0001-7962-0517 AD - Center for Translational Cancer Research, Institute of Biosciences and Technology, College of Medicine, Texas A&M University, Houston, Texas, United States of America. AD - Department of Medical Physiology, College of Medicine, Texas A&M University, Temple, Texas, United States of America. LA - eng GR - R01 GM112003/GM/NIGMS NIH HHS/United States GR - R21 GM126532/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20181108 PL - United States TA - PLoS Biol JT - PLoS biology JID - 101183755 RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Metalloproteins) RN - 0 (P62 protein, human) RN - 0 (PDCD10 protein, human) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA-Binding Proteins) RN - 0 (TRIM59 protein, human) RN - 0 (Tripartite Motif Proteins) SB - IM CIN - Autophagy. 2019 Apr;15(4):747-749. PMID: 30653426 MH - Adult MH - Animals MH - Apoptosis Regulatory Proteins/genetics/*metabolism/physiology MH - Autophagy/physiology MH - Breast Neoplasms/genetics/metabolism MH - Cell Line, Tumor MH - Cell Movement/genetics/physiology MH - Cell Proliferation MH - Female MH - Gene Expression Regulation, Neoplastic/genetics MH - HEK293 Cells MH - Humans MH - Intracellular Signaling Peptides and Proteins MH - Membrane Proteins/*genetics/*metabolism/*physiology MH - Metalloproteins/*genetics/metabolism/*physiology MH - Mice MH - Mice, Inbred NOD MH - Neoplasm Metastasis/pathology MH - Proto-Oncogene Proteins/genetics/*metabolism/physiology MH - RNA-Binding Proteins/physiology MH - Signal Transduction MH - Tripartite Motif Proteins MH - Ubiquitination MH - Xenograft Model Antitumor Assays PMC - PMC6245796 COIS- The authors have declared that no competing interests exist. EDAT- 2018/11/09 06:00 MHDA- 2019/06/18 06:00 PMCR- 2018/11/08 CRDT- 2018/11/09 06:00 PHST- 2018/07/30 00:00 [received] PHST- 2018/10/23 00:00 [accepted] PHST- 2018/11/20 00:00 [revised] PHST- 2018/11/09 06:00 [pubmed] PHST- 2019/06/18 06:00 [medline] PHST- 2018/11/09 06:00 [entrez] PHST- 2018/11/08 00:00 [pmc-release] AID - PBIOLOGY-D-18-00325 [pii] AID - 10.1371/journal.pbio.3000051 [doi] PST - epublish SO - PLoS Biol. 2018 Nov 8;16(11):e3000051. doi: 10.1371/journal.pbio.3000051. eCollection 2018 Nov.