Abstract
Colorectal cancer (CRC) is the third most common cancer in the world and distant metastasis is the leading cause of death among CRC patients. However, the underlying mechanisms of distant metastasis remain largely unknown. Amplification of 8q24 is a common chromosomal abnormality in CRC. In the present study, a putative oncogene at 8q24, TRIB1, was characterized for its role in CRC metastasis and underlying molecular mechanisms. Higher expression of TRIB1 protein was detected in 58/83 (69.9%) of CRC tissues, compared with adjacent non-tumor tissues. Moreover, the expression of TRIB1 was significantly associated with distant metastasis (P=0.043) and advanced staging (P=0.008) in CRC tissues. TRIB1 overexpression was also correlated with poor prognosis in CRC patients as analyzed in PrognoScan database. In addition, elevated expression of TRIB1 promoted CRC cell motility and adhesive ability, while silencing of TRIB1 reduced those effects. Further study revealed that TRIB1-mediated migration and invasion of CRC cells required up-regulation of MMP-2 through the activation of FAK/Src and ERK pathway. Collectively, the results suggest that TRIB1 promotes CRC cell motility by activation MMP-2 via the FAK/Src and ERK pathways. It may provide a potential diagnostic and therapeutic target for CRC.
Highlights
Colorectal cancer (CRC) is the second most common cancer in females and the third in males, with about 1.4 million cases and 693,900 deaths occurring globally in 2012 [1]
FAK inhibitor and Src inhibitor used in Tribbles pseudokinase 1 (TRIB1)-expression cells remarkably inhibited MMP-2 expression and reduced the migratory and invasive abilities of CRC cells (Figure 5C-5F). These results demonstrate that TRIB1 activates the FAK/Src and ERK pathways to up-regulate MMP-2 expression and facilitate CRC cell motility
Our colleagues identified that 8q24 was amplified through Double minute chromosomes (DMs) in CRC cells [5]
Summary
Colorectal cancer (CRC) is the second most common cancer in females and the third in males, with about 1.4 million cases and 693,900 deaths occurring globally in 2012 [1]. The major cause of death in CRC patients is distant metastasis. Tumors that are confined within the wall of colon (stages I and II) are curable by surgical excision, and approximately 73% of CRC cases with lymph node metastasis (stage III) are curable by surgery combined with adjuvant chemotherapy. Patients with distant metastasis are usually incurable, survival has been improved by recent advances in chemotherapy [2]. Double minute chromosomes (DMs) are small, paired, acentric extrachromosomal structures. They are considered to be hallmarks of gene amplification [3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
