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

162 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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Morishita, A., Zaidi, M. R., Mitoro, A., Sankarasharma, D., Szabolcs, M., Okada, Y., D'Armiento, J., & 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