Reprogramming lung cancer cells can revert metastasis: KAIST

Korea Advanced Institute of Science & Technology (KAIST) said on Monday that its researchers published a study on a technology that can change the properties of lung cancer cells to revert metastasis and lower drug resistance.

The epithelial-to-mesenchymal transition (EMT) of primary cancer leads to various malignant traits such as cancer cell migration and infiltration, changes in reactivity to chemotherapy treatment, enhanced stem cell capability, and cancer metastasis. Thus, previous research has attempted to remove or lower the metastatic ability of cancer cells by blocking or reversing EMT. However, achieving complete EMT reversal (rEMT) remains a challenge as cancer cells often transition to hybrid EMT states with high metastatic potential.

Accordingly, a research team led by Professor Cho Kwang-hyun of the Department of Bio and Brain Engineering at KAIST developed a new EMT reversal technology that can reprogram lung cancer cells to remove high plasticity and metastatic ability and increase the reactivity of chemotherapy.

They established a mathematical model of gene regulation networks that plays the primary role in driving rEMT without hybrid properties and applied large-scale computer simulation analysis. Consequently, they identified three key molecular targets that can reverse lung cancer cells including p53, a cancer suppressor protein, SMAD4, a protein included in the SMAD group as a representative signaling mediator that regulates EMT, and ERK1/2, a regulator involved in cell growth and differentiation.

They found that perturbation of one of these proteins could not completely revert EMT but inhibition of both SMAD4 and ERK signaling along with p53 activation induced rEMT in cancer cells even with TGF-β stimulation and also restored chemosensitivity.

"We have proposed a new treatment strategy to improve the prognosis of cancer patients by successfully reversing lung cancer cells with the high metastatic ability and drug resistance to epithelial cells that are sensitive to chemotherapy," said Professor Cho.

He went on to say that these results represent the third achievement in the development of reversible technology for cancer cells as the team previously successfully reprogrammed colon and breast cancer cells.