ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer
Abstract Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04862-1 |
| _version_ | 1828369604264591360 |
|---|---|
| author | Eun-Ji Lim Jae-Hyeok Kang Yeon-Ju Kim Seungmo Kim Su-Jae Lee |
| author_facet | Eun-Ji Lim Jae-Hyeok Kang Yeon-Ju Kim Seungmo Kim Su-Jae Lee |
| author_sort | Eun-Ji Lim |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell–cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC. |
| first_indexed | 2024-04-14T06:26:39Z |
| format | Article |
| id | doaj.art-053eaa3add874b60aa6726247dd094c6 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-14T06:26:39Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-053eaa3add874b60aa6726247dd094c62022-12-22T02:07:47ZengNature Publishing GroupCell Death and Disease2041-48892022-04-0113411110.1038/s41419-022-04862-1ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancerEun-Ji Lim0Jae-Hyeok Kang1Yeon-Ju Kim2Seungmo Kim3Su-Jae Lee4Department of Life Science, Research Institute for Natural Sciences, Hanyang UniversityDepartment of Life Science, Research Institute for Natural Sciences, Hanyang UniversityDepartment of Life Science, Research Institute for Natural Sciences, Hanyang UniversityDepartment of Life Science, Research Institute for Natural Sciences, Hanyang UniversityDepartment of Life Science, Research Institute for Natural Sciences, Hanyang UniversityAbstract Colorectal cancer (CRC) has a 5-year survival rate of <10%, as it can metastasize to the lungs and liver. Anticancer drugs and targeted therapies used to treat metastatic colorectal cancer have insufficient therapeutic efficacy and are associated with complications. Therefore, research to develop new targeted therapeutics is necessary. Here, we present a novel discovery that intracellular adhesion molecule-1 (ICAM-1) is a potential therapeutic target to enhance therapeutic effectiveness for CRC. ICAM-1 is an important regulator of cell–cell interactions and recent studies have shown that it promotes malignancy in several carcinomas. However, little is known about its effect on CRC. Therefore, we conducted a study to define the mechanism by which ICAM-1 acts. ICAM-1 is phosphorylated by tyrosine-protein kinase Met (c-MET), and phosphorylated ICAM-1 can interact with SRC to increase SRC activity. Consequently, ICAM-1 may further accelerate SRC signaling, promoting the malignant potential of cancer. In addition, treatment with antibodies targeting ICAM-1 showed excellent therapeutic effects in reducing metastasis and angiogenesis. These findings suggest for the first time that ICAM-1 is an important adapter protein capable of mediating the c-MET-SRC signaling axis. Therefore, ICAM-1 can be used as a novel therapeutic target and a metastatic marker for CRC.https://doi.org/10.1038/s41419-022-04862-1 |
| spellingShingle | Eun-Ji Lim Jae-Hyeok Kang Yeon-Ju Kim Seungmo Kim Su-Jae Lee ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer Cell Death and Disease |
| title | ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer |
| title_full | ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer |
| title_fullStr | ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer |
| title_full_unstemmed | ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer |
| title_short | ICAM-1 promotes cancer progression by regulating SRC activity as an adapter protein in colorectal cancer |
| title_sort | icam 1 promotes cancer progression by regulating src activity as an adapter protein in colorectal cancer |
| url | https://doi.org/10.1038/s41419-022-04862-1 |
| work_keys_str_mv | AT eunjilim icam1promotescancerprogressionbyregulatingsrcactivityasanadapterproteinincolorectalcancer AT jaehyeokkang icam1promotescancerprogressionbyregulatingsrcactivityasanadapterproteinincolorectalcancer AT yeonjukim icam1promotescancerprogressionbyregulatingsrcactivityasanadapterproteinincolorectalcancer AT seungmokim icam1promotescancerprogressionbyregulatingsrcactivityasanadapterproteinincolorectalcancer AT sujaelee icam1promotescancerprogressionbyregulatingsrcactivityasanadapterproteinincolorectalcancer |