한빛사논문
- 조회1,264
Namhee Kim1†, Chae Young Hwang1,2†, Taeyoung Kim1, Hyunjin Kim1, Kwang-Hyun Cho1*
1Laboratory for Systems Biology and Bio-inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology(KAIST), Daejeon 34141, Republic of Korea
2Aventi Inc. Daejeon 34141, Republic of Korea
†These authors contributed equally to this work.
*Corresponding Author: Kwang-Hyun Cho
Abstract
The epithelial-to-mesenchymal transition (EMT) of primary cancer contributes to the acquisition of lethal properties, including metastasis and drug resistance. Blocking or reversing EMT could be an effective strategy to improve cancer treatment. However, it is still unclear how to achieve complete EMT reversal (rEMT) as cancer cells often transition to hybrid EMT states with high metastatic potential. To tackle this problem, we employed a systems biology approach and identified a core-regulatory circuit that plays the primary role in driving rEMT without hybrid properties. Perturbation of any single-node was not sufficient to completely revert EMT. Inhibition of both SMAD4 and ERK signaling along with p53 activation could induce rEMT in cancer cells even with TGF-β stimulation, a primary inducer of EMT. Induction of rEMT in lung cancer cells with the triple combination approach restored chemosensitivity. This cell-fate reprogramming strategy based on attractor landscapes revealed potential therapeutic targets that can eradicate metastatic potential by subverting EMT while avoiding hybrid states.
논문정보
- Research article
- 2023년 01월 (BRIC 등록일 2023-01-30)
- 국내 연구진
- 생명과학 > 생물공학
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