A Forkhead Box ProteinC2 Inhibitor: Targeting Epithelial-Mesenchymal Transition and Cancer Metastasis

Maria Castaneda, Luxi Chen, Lagnajeet Pradhan, Shichang Li, Ruba Zein, Yeongju Lee, Hyun Suk Lim, Hyun Joo Nam, Jiyong Lee

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The epithelial-mesenchymal transition (EMT) has been suggested as a new target for therapeutic intervention of metastatic cancer. Forkhead box proteinC2 (FOXC2) is known to be necessary for initiating and maintaining EMT, and therefore bestows on cancer cells metastatic and cancer stem cell (CSC)-like phenotypes, allowing cells to acquire higher motility, invasiveness, self-renewal, and therapy resistance. Here, we describe the first inhibitor of FOXC2, MC-1-F2. MC-1-F2 was able to induce cadherin switching and reverse EMT through the degradation of FOXC2 and blocking of its nuclear localization. In addition, MC-1-F2 was very effective in inhibiting cancer cell migration and invasion. As the first small-molecule inhibitor of FOXC2 and the first compound targeting EMT-associated transcription factor, MC-1-F2 will pave the way for a new anticancer therapeutic agent targeting metastatic cancer and help to elucidate the network of EMT signaling pathways.

Original languageEnglish (US)
JournalChemBioChem
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Keywords

  • Cancer metastasis
  • Combinatorial chemistry
  • Drug discovery
  • Epithelial-mesenchymal transition
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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    Castaneda, M., Chen, L., Pradhan, L., Li, S., Zein, R., Lee, Y., Lim, H. S., Nam, H. J., & Lee, J. (Accepted/In press). A Forkhead Box ProteinC2 Inhibitor: Targeting Epithelial-Mesenchymal Transition and Cancer Metastasis. ChemBioChem. https://doi.org/10.1002/cbic.201800022