Abstract
B7-H3, first recognized as a co-stimulatory molecule, is abnormally expressed in cancer tissues and is associated with cancer metastasis and a poor prognosis. However, as an initial event of metastasis, the relationship between the Epithelial–Mesenchymal Transition (EMT) in cancer cells and B7-H3 has still not been investigated. In this study, we first analyzed B7-H3 expression by immunohistochemistry in colorectal cancer tissues. B7-H3 was expressed in the cancer cell membrane and was associated with the T stage of colorectal cancer; it also showed a positive correlation with MMP2 and MMP9 expression in cancer tissues. Over-expression of B7-H3 in SW480 cells allowed cancer cells to invade and metastasize more than the control cells, whereas invasion and metastasis capabilities were decreased after B7-H3 was knocked down in Caco-2 cells. We further showed that B7-H3 down-regulated the expression of E-cadherin and β-catenin and up-regulated N-cadherin and Vimentin expression, implying that B7-H3 promoted the EMT in colorectal cancer cells. We also checked another character of the EMT, the stemness of cancer cells. CD133, CD44 and Oct4 were significantly elevated after the SW480 cells were transfected with B7-H3 and reduced in Caco-2 cells after B7-H3 was inhibited. In subsequent studies, we proved that B7-H3 upregulated the expression of Smad1 via PI3K-Akt. In conclusion, B7-H3 promotes the EMT in colorectal cancer cells by activating the PI3K-Akt pathway and upregulating the expression of Smad1.
Highlights
Colorectal cancer is the third most diagnosed cause of cancer death in the world [1]
There were no significant differences in the patients’ gender, age and regional lymph node metastasis among the four groups, but B7-H3 overwww.impactjournals.com/oncotarget expression increased the T stage of patients (p < 0.001) (Table 1). These results indicated that the expression of B7-H3 in the patients’ colorectal cancer tumor tissues was obviously associated with the depth of cancer invasion but did not have a close relationship with regional lymph node metastasis
We proved that B7-H3 was co-expressed with MMP2 and MMP9 in colorectal cancer patients
Summary
Colorectal cancer is the third most diagnosed cause of cancer death in the world [1]. During the whole process of these diseases, approximately 50% of patients have liver, lung or other organ metastases, and 20% patients already have liver metastases when their colorectal cancer is diagnosed [2]. The process of cancer metastasis can be divided into six sequential steps, including isolation from the cancer tissue, intravasation, survival in the circulatory system, extravasation, homing, and colonization. The cancer cells show high plasticity, including morphological and phenotypical conversions, named the epithelial to mesenchymal transition (EMT) [4, 5]. The mesenchymal to epithelial transition (MET) describes the reverse process. The cancer cells undergoing EMT or MET are influenced by their microenvironment [6], hypoxia [7], cytokines [8], etc
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
