HMGA2 is a driver of tumor metastasis

Asahiro Morishita, M. Raza Zaidi, Akira Mitoro, Devipriya Sankarasharma, Matthias Szabolcs, Yasunori Okada, Jeanine D'Armiento, Kiran Chada

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression ofHMGA2 in epithelial cells induces epithelial-mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known about in vivo modulation of HMGA2 and its effector functions in tumor metastasis. Here, we report that HMGA2 loss of function in a mouse model of cancer reduces tumor multiplicity.HMGA2-positive cellswere identified at the invasive front of human andmouse tumors. In addition, in a mouse allograft model, HMGA2 overexpression converted nonmetastatic 4TO7 breast cancer cells to metastatic cells that homed specifically to liver. Interestingly, expression of HMGA2 enhanced TGFb signaling by activating expression of the TGFβ type II receptor, which also localized to the invasive front of tumors. Together our results argued that HMGA2 plays a critical role in EMT by activating the TGFβ signaling pathway, thereby inducing invasion and metastasis of human epithelial cancers.

Original languageEnglish
Pages (from-to)4289-4299
Number of pages11
JournalCancer Research
Volume73
Issue number14
DOIs
Publication statusPublished - 2013 Jul 15

Fingerprint

Neoplasm Metastasis
Neoplasms
Epithelial-Mesenchymal Transition
Mesoderm
Chromatin
Allografts
Carrier Proteins
Epithelial Cells
Breast Neoplasms
Liver

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Morishita, A., Zaidi, M. R., Mitoro, A., Sankarasharma, D., Szabolcs, M., Okada, Y., ... Chada, K. (2013). HMGA2 is a driver of tumor metastasis. Cancer Research, 73(14), 4289-4299. https://doi.org/10.1158/0008-5472.CAN-12-3848

HMGA2 is a driver of tumor metastasis. / Morishita, Asahiro; Zaidi, M. Raza; Mitoro, Akira; Sankarasharma, Devipriya; Szabolcs, Matthias; Okada, Yasunori; D'Armiento, Jeanine; Chada, Kiran.

In: Cancer Research, Vol. 73, No. 14, 15.07.2013, p. 4289-4299.

Research output: Contribution to journalArticle

Morishita, A, Zaidi, MR, Mitoro, A, Sankarasharma, D, Szabolcs, M, Okada, Y, D'Armiento, J & Chada, K 2013, 'HMGA2 is a driver of tumor metastasis', Cancer Research, vol. 73, no. 14, pp. 4289-4299. https://doi.org/10.1158/0008-5472.CAN-12-3848
Morishita A, Zaidi MR, Mitoro A, Sankarasharma D, Szabolcs M, Okada Y et al. HMGA2 is a driver of tumor metastasis. Cancer Research. 2013 Jul 15;73(14):4289-4299. https://doi.org/10.1158/0008-5472.CAN-12-3848
Morishita, Asahiro ; Zaidi, M. Raza ; Mitoro, Akira ; Sankarasharma, Devipriya ; Szabolcs, Matthias ; Okada, Yasunori ; D'Armiento, Jeanine ; Chada, Kiran. / HMGA2 is a driver of tumor metastasis. In: Cancer Research. 2013 ; Vol. 73, No. 14. pp. 4289-4299.
@article{ea648f8a48ef421889f1510f5b037840,
title = "HMGA2 is a driver of tumor metastasis",
abstract = "The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression ofHMGA2 in epithelial cells induces epithelial-mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known about in vivo modulation of HMGA2 and its effector functions in tumor metastasis. Here, we report that HMGA2 loss of function in a mouse model of cancer reduces tumor multiplicity.HMGA2-positive cellswere identified at the invasive front of human andmouse tumors. In addition, in a mouse allograft model, HMGA2 overexpression converted nonmetastatic 4TO7 breast cancer cells to metastatic cells that homed specifically to liver. Interestingly, expression of HMGA2 enhanced TGFb signaling by activating expression of the TGFβ type II receptor, which also localized to the invasive front of tumors. Together our results argued that HMGA2 plays a critical role in EMT by activating the TGFβ signaling pathway, thereby inducing invasion and metastasis of human epithelial cancers.",
author = "Asahiro Morishita and Zaidi, {M. Raza} and Akira Mitoro and Devipriya Sankarasharma and Matthias Szabolcs and Yasunori Okada and Jeanine D'Armiento and Kiran Chada",
year = "2013",
month = "7",
day = "15",
doi = "10.1158/0008-5472.CAN-12-3848",
language = "English",
volume = "73",
pages = "4289--4299",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "14",

}

TY - JOUR

T1 - HMGA2 is a driver of tumor metastasis

AU - Morishita, Asahiro

AU - Zaidi, M. Raza

AU - Mitoro, Akira

AU - Sankarasharma, Devipriya

AU - Szabolcs, Matthias

AU - Okada, Yasunori

AU - D'Armiento, Jeanine

AU - Chada, Kiran

PY - 2013/7/15

Y1 - 2013/7/15

N2 - The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression ofHMGA2 in epithelial cells induces epithelial-mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known about in vivo modulation of HMGA2 and its effector functions in tumor metastasis. Here, we report that HMGA2 loss of function in a mouse model of cancer reduces tumor multiplicity.HMGA2-positive cellswere identified at the invasive front of human andmouse tumors. In addition, in a mouse allograft model, HMGA2 overexpression converted nonmetastatic 4TO7 breast cancer cells to metastatic cells that homed specifically to liver. Interestingly, expression of HMGA2 enhanced TGFb signaling by activating expression of the TGFβ type II receptor, which also localized to the invasive front of tumors. Together our results argued that HMGA2 plays a critical role in EMT by activating the TGFβ signaling pathway, thereby inducing invasion and metastasis of human epithelial cancers.

AB - The non-histone chromatin-binding protein HMGA2 is expressed predominantly in the mesenchyme before its differentiation, but it is also expressed in tumors of epithelial origin. Ectopic expression ofHMGA2 in epithelial cells induces epithelial-mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characters in tumor cells. However, little is known about in vivo modulation of HMGA2 and its effector functions in tumor metastasis. Here, we report that HMGA2 loss of function in a mouse model of cancer reduces tumor multiplicity.HMGA2-positive cellswere identified at the invasive front of human andmouse tumors. In addition, in a mouse allograft model, HMGA2 overexpression converted nonmetastatic 4TO7 breast cancer cells to metastatic cells that homed specifically to liver. Interestingly, expression of HMGA2 enhanced TGFb signaling by activating expression of the TGFβ type II receptor, which also localized to the invasive front of tumors. Together our results argued that HMGA2 plays a critical role in EMT by activating the TGFβ signaling pathway, thereby inducing invasion and metastasis of human epithelial cancers.

UR - http://www.scopus.com/inward/record.url?scp=84880878241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880878241&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-12-3848

DO - 10.1158/0008-5472.CAN-12-3848

M3 - Article

C2 - 23722545

AN - SCOPUS:84880878241

VL - 73

SP - 4289

EP - 4299

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 14

ER -