MYC is a crucial mediator of TGFβ-induced invasion in basal breast cancer

Magdalena A. Cichon, Megan E. Moruzzi, Tiziana A. Shqau, Erin Miller, Christine Mehner, Stephen P. Ethier, John A III Copland, Evette S Radisky, Derek C Radisky

Research output: Contribution to journalArticle

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Abstract

Basal subtype breast cancers have a particularly poor prognosis, with high invasiveness and resistance to most targeted therapies. TGFβ and MYC drive central features of basal breast cancer: TGFβ is an autocrine and paracrine signaling factor that drives cell invasion and metastasis, and MYC is a central regulator of cellular proliferation that is upregulated in many cancer types. We show here that genetic or pharmacologic inhibition of MYC in MCF10A basal breast cells results in increased sensitivity to TGFβ-stimulated invasion and metastasis and also show that this signaling loop is dependent on activation of SRC. Analysis of human breast cancer datasets and additional experiments with breast cancer cell lines further suggest the relevance of this signaling loop in basal, but not luminal, breast cancers. Our results imply precaution should be taken when utilizing therapeutic inhibitors of MYC with basal breast cancer patients as this could lead to increased metastasis; however, simultaneous pharmacologic inhibition of SRC and MYC for these patients could facilitate the antiproliferative effects of MYC inhibition while blocking the consequent promotion of metastasis.

Original languageEnglish (US)
Pages (from-to)3520-3530
Number of pages11
JournalCancer Research
Volume76
Issue number12
DOIs
StatePublished - Jun 15 2016

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Breast Neoplasms
Neoplasm Metastasis
Autocrine Communication
Paracrine Communication
Breast
Cell Proliferation
Cell Line
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Cichon, M. A., Moruzzi, M. E., Shqau, T. A., Miller, E., Mehner, C., Ethier, S. P., ... Radisky, D. C. (2016). MYC is a crucial mediator of TGFβ-induced invasion in basal breast cancer. Cancer Research, 76(12), 3520-3530. https://doi.org/10.1158/0008-5472.CAN-15-3465

MYC is a crucial mediator of TGFβ-induced invasion in basal breast cancer. / Cichon, Magdalena A.; Moruzzi, Megan E.; Shqau, Tiziana A.; Miller, Erin; Mehner, Christine; Ethier, Stephen P.; Copland, John A III; Radisky, Evette S; Radisky, Derek C.

In: Cancer Research, Vol. 76, No. 12, 15.06.2016, p. 3520-3530.

Research output: Contribution to journalArticle

Cichon MA, Moruzzi ME, Shqau TA, Miller E, Mehner C, Ethier SP et al. MYC is a crucial mediator of TGFβ-induced invasion in basal breast cancer. Cancer Research. 2016 Jun 15;76(12):3520-3530. https://doi.org/10.1158/0008-5472.CAN-15-3465
Cichon, Magdalena A. ; Moruzzi, Megan E. ; Shqau, Tiziana A. ; Miller, Erin ; Mehner, Christine ; Ethier, Stephen P. ; Copland, John A III ; Radisky, Evette S ; Radisky, Derek C. / MYC is a crucial mediator of TGFβ-induced invasion in basal breast cancer. In: Cancer Research. 2016 ; Vol. 76, No. 12. pp. 3520-3530.
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