MIRO2 promotes cancer invasion and metastasis via MYO9B suppression of RhoA activity

被引：2

作者：

Boulton, Dillon P. ^{[1
,2
]}

Hughes, Connor J. ^{[1
,2
]}

Vaira, Valentina ^{[3
,4
]}

Del Gobbo, Alessandro ^{[4
]}

Palleschi, Alessandro ^{[3
,5
]}

Locatelli, Marco ^{[3
,6
]}

Danis, Etienne ^{[7
,8
]}

Raza, Masoom ^{[1
]}

Neumann, Andrew J. ^{[9
,10
]}

Purdy, Stephen Connor ^{[1
,11
]}

Lerma, Raymundo ^{[1
,10
]}

Meshki, John ^{[1
]}

Ford, Heide L. ^{[1
,8
]}

Prekeris, Rytis ^{[9
]}

Morrissey, Colm ^{[12
]}

Caino, M. Cecilia ^{[1
,8
]}

机构：

[1] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA

[2] Univ Colorado, Pharmacol Grad Program, Aurora, CO 80045 USA

[3] Univ Milan, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy

[4] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Div Pathol, I-20122 Milan, Italy

[5] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Div Thorac Surg & Lung Transplantat, I-20122 Milan, Italy

[6] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Div Neurosurg, I-20122 Milan, Italy

[7] Univ Colorado, Bioinformat & Biostat Shared Resource Core, Aurora, CO 80045 USA

[8] Univ Colorado Anschutz Med Campus, Univ Colorado Canc Ctr, Aurora, CO 80045 USA

[9] Univ Colorado Anschutz Med Campus, Dept Cell & Dev Biol, Aurora, CO 80045 USA

[10] Univ Colorado, Mol Biol Grad Program, Aurora, CO 80045 USA

[11] Univ Colorado, Canc Biol Grad Program, Aurora, CO 80045 USA

[12] Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA

来源：

CELL REPORTS | 2025年 / 44卷 / 01期

关键词：

MYOSIN-IXB; GTPASES; ROLES; OVEREXPRESSION; MIGRATION; PROTEIN; MOTOR;

D O I：

10.1016/j.celrep.2024.115120

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Metastasis to vital organs remains the leading cause of cancer-related deaths, emphasizing an urgent need for actionable targets in advanced-stage cancer. The role of mitochondrial Rho GTPase 2 (MIRO2) in prostate cancer growth was recently reported; however, whether MIRO2 is important for additional steps in the metastatic cascade is unknown. Here, we show that knockdown of MIRO2 ubiquitously reduces tumor cell invasion in vitro and suppresses metastatic burden in prostate and breast cancer mouse models. Mechanistically, depletion of MIRO2's binding partner-unconventional myosin 9B (MYO9B)-reduces tumor cell invasion and phenocopies MIRO2 depletion, which in turn results in increased active RhoA. Furthermore, dual ablation of MIRO2 and RhoA fully rescues tumor cell invasion, and MIRO2 is required for MYO9B-driven invasion. Taken together, we show that MIRO2 supports invasion and metastasis through cooperation with MYO9B, underscoring a potential targetable pathway for patients with advanced disease.

引用

页数：24

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