Suppression of miRNA-708 by Polycomb Group Promotes Metastases by Calcium-Induced Cell Migration

Seongho Ryu; Kevin McDonnell; Hyejin Choi; Dingcheng Gao; Mary Hahn; Natasha Joshi; Sun Mi Park; Raul Catena; Yoonkyung Do; Jacqueline Brazin; Linda T. Vahdat; Randi B. Silver; Vivek Mittal

doi:10.1016/j.ccr.2012.11.019

Suppression of miRNA-708 by Polycomb Group Promotes Metastases by Calcium-Induced Cell Migration

Seongho Ryu, Kevin McDonnell, Hyejin Choi, Dingcheng Gao, Mary Hahn, Natasha Joshi, Sun Mi Park, Raul Catena, Yoonkyung Do, Jacqueline Brazin, Linda T. Vahdat, Randi B. Silver, Vivek Mittal

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

Abstract

The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.

Original language	English (US)
Pages (from-to)	63-76
Number of pages	14
Journal	Cancer Cell
Volume	23
Issue number	1
DOIs	https://doi.org/10.1016/j.ccr.2012.11.019
State	Published - Jan 14 2013

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2012.11.019

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title = "Suppression of miRNA-708 by Polycomb Group Promotes Metastases by Calcium-Induced Cell Migration",

abstract = "The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.",

author = "Seongho Ryu and Kevin McDonnell and Hyejin Choi and Dingcheng Gao and Mary Hahn and Natasha Joshi and Park, {Sun Mi} and Raul Catena and Yoonkyung Do and Jacqueline Brazin and Vahdat, {Linda T.} and Silver, {Randi B.} and Vivek Mittal",

note = "Funding Information: We thank Anna Durrans and Kari Fischer for comments on the manuscript. This work was supported by funding from The Neuberger Berman Lung Cancer Laboratory, The Robert I. Goldman Foundation, and the Cornell Center on the Microenvironment and Metastasis through Award Number U54CA143876 from the NCI to V.M. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2013",

month = jan,

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doi = "10.1016/j.ccr.2012.11.019",

language = "English (US)",

volume = "23",

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AU - Ryu, Seongho

AU - McDonnell, Kevin

AU - Choi, Hyejin

AU - Gao, Dingcheng

AU - Hahn, Mary

AU - Joshi, Natasha

AU - Park, Sun Mi

AU - Catena, Raul

AU - Do, Yoonkyung

AU - Brazin, Jacqueline

AU - Vahdat, Linda T.

AU - Silver, Randi B.

AU - Mittal, Vivek

N1 - Funding Information: We thank Anna Durrans and Kari Fischer for comments on the manuscript. This work was supported by funding from The Neuberger Berman Lung Cancer Laboratory, The Robert I. Goldman Foundation, and the Cornell Center on the Microenvironment and Metastasis through Award Number U54CA143876 from the NCI to V.M. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2013/1/14

Y1 - 2013/1/14

N2 - The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.

AB - The progression of cancer to metastatic disease is a major cause of death. We identified miR-708 being transcriptionally repressed by polycomb repressor complex 2-induced H3K27 trimethylation in metastatic breast cancer. miR-708 targets the endoplasmic reticulum protein neuronatin to decrease intracellular calcium level, resulting in reduction of activation of ERK and FAK, decreased cell migration, and impaired metastases. Ectopic expression of neuronatin refractory to suppression by miR-708 rescued cell migration and metastasis defects. In patients with breast cancer, miR-708 expression was decreased in lymph node and distal metastases, suggesting a metastasis-suppressive role. Our findings uncover a mechanistic role for miR-708 in metastasis and provide a rationale for developing miR-708 as a therapeutic agent against metastatic breast cancer.

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Suppression of miRNA-708 by Polycomb Group Promotes Metastases by Calcium-Induced Cell Migration

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