ID genes mediate tumor reinitiation during breast cancer lung metastasis

Research output: Contribution to journalArticle

Gaorav P. Gupta, Jonathan Perk, Swarnali Acharyya, Paola De Candia, Vivek Mittal, Katia Todorova-Manova, William L. Gerald, Edi Brogi, Robert Benezra, Joan Massagué

The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family member Id3 are required for tumor initiating functions, both in the context of primary tumor formation and during metastatic colonization of the lung microenvironment. In vivo characterization of lung metastatic progression reveals that Id1 and Id3 facilitate sustained proliferation during the early stages of metastatic colonization, subsequent to extravasation into the lung parenchyma. These results shed light on the proliferative mechanisms that initiate metastatic colonization, and they implicate Id1 and Id3 as mediators of this malignant function in the TN subgroup of breast cancers.

Original languageEnglish
Pages (from-to)19506-19511
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number49
DOIs
StatePublished - Dec 4 2007

PMID: 18048329

PMCID: PMC2148319

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ID genes mediate tumor reinitiation during breast cancer lung metastasis. / Gupta, Gaorav P.; Perk, Jonathan; Acharyya, Swarnali; De Candia, Paola; Mittal, Vivek; Todorova-Manova, Katia; Gerald, William L.; Brogi, Edi; Benezra, Robert; Massagué, Joan.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 49, 04.12.2007, p. 19506-19511.

Research output: Contribution to journalArticle

Harvard

Gupta, GP, Perk, J, Acharyya, S, De Candia, P, Mittal, V, Todorova-Manova, K, Gerald, WL, Brogi, E, Benezra, R & Massagué, J 2007, 'ID genes mediate tumor reinitiation during breast cancer lung metastasis' Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19506-19511. https://doi.org/10.1073/pnas.0709185104

APA

Gupta, G. P., Perk, J., Acharyya, S., De Candia, P., Mittal, V., Todorova-Manova, K., ... Massagué, J. (2007). ID genes mediate tumor reinitiation during breast cancer lung metastasis. Proceedings of the National Academy of Sciences of the United States of America, 104(49), 19506-19511. https://doi.org/10.1073/pnas.0709185104

Vancouver

Gupta GP, Perk J, Acharyya S, De Candia P, Mittal V, Todorova-Manova K et al. ID genes mediate tumor reinitiation during breast cancer lung metastasis. Proceedings of the National Academy of Sciences of the United States of America. 2007 Dec 4;104(49):19506-19511. https://doi.org/10.1073/pnas.0709185104

Author

Gupta, Gaorav P. ; Perk, Jonathan ; Acharyya, Swarnali ; De Candia, Paola ; Mittal, Vivek ; Todorova-Manova, Katia ; Gerald, William L. ; Brogi, Edi ; Benezra, Robert ; Massagué, Joan. / ID genes mediate tumor reinitiation during breast cancer lung metastasis. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 49. pp. 19506-19511.

BibTeX

@article{8e6402809efc4f20a03a4ab5a41b4937,
title = "ID genes mediate tumor reinitiation during breast cancer lung metastasis",
abstract = "The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family member Id3 are required for tumor initiating functions, both in the context of primary tumor formation and during metastatic colonization of the lung microenvironment. In vivo characterization of lung metastatic progression reveals that Id1 and Id3 facilitate sustained proliferation during the early stages of metastatic colonization, subsequent to extravasation into the lung parenchyma. These results shed light on the proliferative mechanisms that initiate metastatic colonization, and they implicate Id1 and Id3 as mediators of this malignant function in the TN subgroup of breast cancers.",
keywords = "Proliferation, Stem cells, Triple negative",
author = "Gupta, {Gaorav P.} and Jonathan Perk and Swarnali Acharyya and {De Candia}, Paola and Vivek Mittal and Katia Todorova-Manova and Gerald, {William L.} and Edi Brogi and Robert Benezra and Joan Massagu{\'e}",
year = "2007",
month = "12",
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doi = "10.1073/pnas.0709185104",
language = "English",
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journal = "Proceedings of the National Academy of Sciences of the United States of America",
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RIS

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T1 - ID genes mediate tumor reinitiation during breast cancer lung metastasis

AU - Gupta, Gaorav P.

AU - Perk, Jonathan

AU - Acharyya, Swarnali

AU - De Candia, Paola

AU - Mittal, Vivek

AU - Todorova-Manova, Katia

AU - Gerald, William L.

AU - Brogi, Edi

AU - Benezra, Robert

AU - Massagué, Joan

PY - 2007/12/4

Y1 - 2007/12/4

N2 - The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family member Id3 are required for tumor initiating functions, both in the context of primary tumor formation and during metastatic colonization of the lung microenvironment. In vivo characterization of lung metastatic progression reveals that Id1 and Id3 facilitate sustained proliferation during the early stages of metastatic colonization, subsequent to extravasation into the lung parenchyma. These results shed light on the proliferative mechanisms that initiate metastatic colonization, and they implicate Id1 and Id3 as mediators of this malignant function in the TN subgroup of breast cancers.

AB - The establishment of distant metastases depends on the capacity of small numbers of cancer cells to regenerate a tumor after entering a target tissue. The mechanisms that confer this capacity remain to be defined. Here we identify a role for the transcriptional inhibitors of differentiation Id1 and Id3 as selective mediators of lung metastatic colonization in the triple negative [TN, i.e., lacking expression of estrogen receptor and progesterone receptor, and lacking Her2 (human epidermal growth factor receptor 2) amplification] subgroup of human breast cancer. Although broad expression of Id1 has recently been documented in tumors of the rare metaplastic subtype, here we report that rare Id1-expressing cells are also present in the more common TN subset of human breast tumors but not in other subtypes. We also provide evidence that Id1 expression is enriched in clinically obtained hormone receptor negative lung metastases. Functional studies demonstrate that Id1 and its closely related family member Id3 are required for tumor initiating functions, both in the context of primary tumor formation and during metastatic colonization of the lung microenvironment. In vivo characterization of lung metastatic progression reveals that Id1 and Id3 facilitate sustained proliferation during the early stages of metastatic colonization, subsequent to extravasation into the lung parenchyma. These results shed light on the proliferative mechanisms that initiate metastatic colonization, and they implicate Id1 and Id3 as mediators of this malignant function in the TN subgroup of breast cancers.

KW - Proliferation

KW - Stem cells

KW - Triple negative

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U2 - 10.1073/pnas.0709185104

DO - 10.1073/pnas.0709185104

M3 - Article

VL - 104

SP - 19506

EP - 19511

JO - Proceedings of the National Academy of Sciences of the United States of America

T2 - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

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