OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathway
Abstract Background Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-024-11925-3 |
| _version_ | 1827327212007718912 |
|---|---|
| author | Yong Tang Yi Liu Xiaobo Wang Haiyang Guo Lin Chen Guangbing Hu Yutong Cui Shiqi Liang Ji Zuo Zichen Luo Xinrui Chen Xianfei Wang |
| author_facet | Yong Tang Yi Liu Xiaobo Wang Haiyang Guo Lin Chen Guangbing Hu Yutong Cui Shiqi Liang Ji Zuo Zichen Luo Xinrui Chen Xianfei Wang |
| author_sort | Yong Tang |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. Methods Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-β/Smad signaling pathway-related proteins was investigated using western blotting. Results In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-βR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-β / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. Conclusion The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-β/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance. |
| first_indexed | 2024-03-07T14:56:48Z |
| format | Article |
| id | doaj.art-c3ff4536f47c474884dd3f9af17dbdb3 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-07T14:56:48Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c3ff4536f47c474884dd3f9af17dbdb32024-03-05T19:22:41ZengBMCBMC Cancer1471-24072024-02-0124111610.1186/s12885-024-11925-3OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathwayYong Tang0Yi Liu1Xiaobo Wang2Haiyang Guo3Lin Chen4Guangbing Hu5Yutong Cui6Shiqi Liang7Ji Zuo8Zichen Luo9Xinrui Chen10Xianfei Wang11Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Radiation Oncology, Chongqing University Cancer HospitalDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, Affiliated Hospital of North Sichuan Medical CollegeAbstract Background Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. Methods Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-β/Smad signaling pathway-related proteins was investigated using western blotting. Results In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-βR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-β / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. Conclusion The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-β/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.https://doi.org/10.1186/s12885-024-11925-3OLFM2EMTTGF-β/Smad signaling pathwayColorectal cancer |
| spellingShingle | Yong Tang Yi Liu Xiaobo Wang Haiyang Guo Lin Chen Guangbing Hu Yutong Cui Shiqi Liang Ji Zuo Zichen Luo Xinrui Chen Xianfei Wang OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathway BMC Cancer OLFM2 EMT TGF-β/Smad signaling pathway Colorectal cancer |
| title | OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathway |
| title_full | OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathway |
| title_fullStr | OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathway |
| title_full_unstemmed | OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathway |
| title_short | OLFM2 promotes epithelial-mesenchymal transition, migration, and invasion in colorectal cancer through the TGF-β/Smad signaling pathway |
| title_sort | olfm2 promotes epithelial mesenchymal transition migration and invasion in colorectal cancer through the tgf β smad signaling pathway |
| topic | OLFM2 EMT TGF-β/Smad signaling pathway Colorectal cancer |
| url | https://doi.org/10.1186/s12885-024-11925-3 |
| work_keys_str_mv | AT yongtang olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT yiliu olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT xiaobowang olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT haiyangguo olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT linchen olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT guangbinghu olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT yutongcui olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT shiqiliang olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT jizuo olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT zichenluo olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT xinruichen olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway AT xianfeiwang olfm2promotesepithelialmesenchymaltransitionmigrationandinvasionincolorectalcancerthroughthetgfbsmadsignalingpathway |