Research Papers:
Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1
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Abstract
Xiao-Hong Liao1,2,3,*, Ye Zhang1,*, Wen-Jie Dong1,2,3, Zhi-Min Shao1,2,3,4,5 and Da-Qiang Li1,2,3,4,5
1Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
2Department of Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China
3Cancer Institute, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China
4Department of Breast Surgery, Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China
5Key Laboratory of Breast Cancer in Shanghai, Shanghai Medical College, Fudan University, Shanghai 200032, China
*These authors contributed equally to this work
Correspondence to:
Zhi-Min Shao, email: [email protected]
Da-Qiang Li, email: [email protected]
Keywords: breast cancer, invasion and metastasis, protein-protein interaction, MORC2, proline-rich domain
Received: April 13, 2017 Accepted: June 05, 2017 Published: June 16, 2017
ABSTRACT
MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein with emerging roles in the regulation of DNA damage response and gene transcription, but its mechanistic role in breast cancer development and progression remains unexplored. Here, we show that MORC2 promoted breast cancer invasion and metastasis and these effects depended on a proline-rich domain (PRD) within its carboxy-terminal region spanning residues 601–734. Induced expression of wild-type MORC2 did not significantly affect cell proliferation and cell-cycle progression, but promoted breast cancer cell migration and invasion in vitro and metastatic lung colonization in vivo. The PRD domain was dispensable for the protein stability and subcellular localization of MORC2, but depletion of the PRD domain substantially suppressed MORC2-mediated migration, invasion, and metastasis. Proteomic and biochemical analyses further demonstrated that wild-type MORC2, but not PRD deletion mutant, interacted with catenin delta 1 (CTNND1), a cadherin-associated protein that participates in tumor invasion and metastasis. Moreover, knockdown of endogenous CTNND1 by short hairpin RNAs suppressed the migratory and invasive potential of MORC2-expressing cells. Taken together, these results suggest that MORC2 promotes breast cancer invasion and metastasis through its PRD domain-mediated interaction with CTNND1.
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