Open AccessEnforced dual‐specificity tyrosine‐regulated kinase 2 expression by adenovirus‐mediated gene transfer inhibits tumor growth and metastasis of colorectal cancer
Author(s) -
Imaizumi Yuta,
Yoshida Saishu,
Kanegae Yumi,
Eto Ken,
Yoshida Kiyotsugu
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15247
Subject(s) - cancer research , metastasis , colorectal cancer , cancer , apoptosis , cell growth , tyrosine kinase , mouse model of colorectal and intestinal cancer , medicine , biology , receptor , biochemistry , genetics
Colorectal cancer is one of the most common gastrointestinal tumors with good outcomes; however, with distant metastasis, the outcomes are poor. Novel treatment methods are urgently needed. Our in vitro studies indicate that dual‐specificity tyrosine‐regulated kinase 2 (DYRK2) functions as a tumor suppressor in colorectal cancer by regulating cell survival, proliferation, and apoptosis induction. In addition, DYRK2 expression is decreased in tumor tissues compared to nontumor tissues in colorectal cancer, indicating a correlation with clinical prognosis. In this context, we devised a novel therapeutic strategy to overexpress DYRK2 in tumors by adenovirus‐mediated gene transfer. The present study shows that overexpression of DYRK2 in colon cancer cell lines by adenovirus inhibits cell proliferation and induces apoptosis in vitro. Furthermore, in mouse subcutaneous xenograft and liver metastasis models, enforced expression of DYRK2 by direct or intravenous injection of adenovirus to the tumor significantly inhibits tumor growth. Taken together, these findings show that adenovirus‐based overexpression of DYRK2 could be a novel gene therapy for liver metastasis of colorectal cancer.