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A Forkhead Box Protein C2 Inhibitor: Targeting Epithelial–Mesenchymal Transition and Cancer Metastasis
Author(s) -
Castaneda Maria,
Chen Luxi,
Pradhan Lagnajeet,
Li Shichang,
Zein Ruba,
Lee Yeongju,
Lim HyunSuk,
Nam HyunJoo,
Lee Jiyong
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800022
Subject(s) - epithelial–mesenchymal transition , cancer research , cancer cell , motility , metastasis , cancer stem cell , transcription factor , cancer , biology , chemistry , stem cell , microbiology and biotechnology , gene , biochemistry , genetics
The epithelial–mesenchymal transition (EMT) has been suggested as a new target for therapeutic intervention of metastatic cancer. Forkhead box protein C2 (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.