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Title 

Recombinant cell-permeable HOXA9 protein inhibits NSCLC cell migration and invasion

 

세포투과성 HOXA9 재조합 단백질 비소세포폐암의 이동 및 전이 억제

Authors 

S L YuHan KooH Y LeeYoung Il YeomDong Chul LeeJ Kang

Publisher 

Springer Verlag (Germany)

Issue Date 

2019

Citation 

CELLULAR ONCOLOGY

Keywords 

Non-small cell lung cancerInvasionMigrationHomeobox A9Cell-penetrating peptide

Abstract 

Purpose Previously, it has been reported that homeobox A9 (HOXA9) protein expression is downregulated in lung cancer cells, and that its expression is inversely correlated with the metastatic potential of lung cancer cells both in vitro and in vivo. As such, HOXA9 shows therapeutic potential. The development of therapeutic strategies based on this protein is, however, limited due to its poor membrane permeability. To overcome this problem, we developed a system to deliver HOXA9 protein into non-small cell lung cancer (NSCLC) cells. Methods First, we constructed a delivery vector expressing polyarginine, a cell-penetrating peptide, as well as HOXA9. The resulting recombinant R10-HOXA9 protein was effectively introduced into A549 and NCI-H1299 NSCLC cells. Next, we examined the roles and molecular mechanisms of recombinant R10-HOXA9 in processes involved in tumor progression. To investigate the therapeutic efficacy of the delivery system, we performed cell motility assays using both in vitro and in vivo experimental models. Results We found that recombinant R10-HOXA9 protein reduced the invasion and migration rate, but not the proliferation rate, of the NSCLC cells tested, both in vitro and in vivo. Treatment of NSCLC cells with recombinant R10-HOXA9 protein led to a significant increase in E-cadherin expression. Conversely, we found that the expression of snail family zinc finger 2 (SLUG), a transcriptional repressor of E-cadherin, was markedly decreased. In an experimental metastatic mouse model, recombinant R10- HOXA9 protein was found to effectively reduce the rate of lung cancer cell motility. Conclusions Our data suggest that the developed cell-permeable R10-HOXA9 system may serve as a useful tool to prevent NSCLC cell migration and invasion.

URI 

https://doi.org/10.1007/s13402-019-00424-4

ISSN 

2211-3428

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-07-10


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