Dataset Information

Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1.

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.

SUBMITTER: Liao XH

PROVIDER: S-EPMC5716704 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1.

Liao Xiao-Hong XH Zhang Ye Y Dong Wen-Jie WJ Shao Zhi-Min ZM Li Da-Qiang DQ

Oncotarget 20170616 58

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 di ...[more]

PMID: 29228664

Similar Datasets

Project description:Tumor invasion and metastasis represent a major unsolved problem in cancer pathogenesis. Recent studies have indicated the involvement of Src-homology 2 domain-containing tyrosine phosphatase 2 (SHP2) in multiple malignancies; however, the role of SHP2 in oral cancer progression has yet to be elucidated. We propose that SHP2 is involved in the progression of oral cancer toward metastasis.SHP2 expression was evaluated in paired oral cancer tissues by using immunohistochemical staining and real-time reverse transcription polymerase chain reaction. Isogenic highly invasive oral cancer cell lines from their respective low invasive parental lines were established using a Boyden chamber assay, and changes in the hallmarks of the epithelial-mesenchymal transition (EMT) were assessed to evaluate SHP2 function. SHP2 activity in oral cancer cells was reduced using si-RNA knockdown or enforced expression of a catalytically deficient mutant to analyze migratory and invasive ability in vitro and metastasis toward the lung in mice in vivo.We observed the significant upregulation of SHP2 in oral cancer tissues and cell lines. Following SHP2 knockdown, the oral cancer cells markedly attenuated migratory and invasion ability. We observed similar results in phosphatase-dead SHP2 C459S mutant expressing cells. Enhanced invasiveness was associated with significant upregulation of E-cadherin, vimentin, Snail/Twist1, and matrix metalloproteinase-2 in the highly invasive clones. In addition, we determined that SHP2 activity is required for the downregulation of phosphorylated ERK1/2, which modulates the downstream effectors, Snail and Twist1 at a transcript level. In lung tissue sections of mice, we observed that HSC3 tumors with SHP2 deletion exhibited significantly reduced metastatic capacity, compared with tumors administered control si-RNA.Our data suggest that SHP2 promotes the invasion and metastasis of oral cancer cells. These results provide a rationale for further investigating the effects of small-molecule SHP2 inhibitors on the progression of oral cancer, and indicate a previously unrecognized SHP2-ERK1/2-Snail/Twist1 pathway that is likely to play a crucial role in oral cancer invasion and metastasis.

Dataset Information

Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1.

Publications

Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets