Research Papers: Immunology:

The co-stimulatory molecule B7-H3 promotes the epithelial-mesenchymal transition in colorectal cancer

Bo Jiang, Ting Zhang, Fen Liu, Zhangzhang Sun, Hanping Shi, Dong Hua and Chen Yang _

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Oncotarget. 2016; 7:31755-31771. https://doi.org/10.18632/oncotarget.9035

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Bo Jiang1, Ting Zhang2, Fen Liu2, Zhangzhang Sun3, Hanping Shi1, Dong Hua3 and Chen Yang4

1 Department of Medical Oncology, Beijing Institute of Translational Medicine, Chinese Academy of Sciences/Cancer Center, Aviation General Hospital, Beijing, China

2 Institute of Cancer, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China

3 Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China

4 Department of Nuclear-Medicine, Suzhou Hospital Affiliated to Nanjing Medical University, Suzhou, Jiangsu, China

Correspondence to:

Bo Jiang, email:

Chen Yang, email:

Keywords: B7-H3, colorectal cancer, epithelial-mesenchymal transition, co-stimulatory molecule, metastasis, Immunology and Microbiology Section, Immune response, Immunity

Received: July 17, 2015 Accepted: March 31, 2016 Published: April 27, 2016


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.

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