2. Academic Validation
  3. Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

Upregulated expression of HOXB7 in intrahepatic cholangiocarcinoma is associated with tumor cell metastasis and poor prognosis

  • Lab Invest. 2019 Jun;99(6):736-748. doi: 10.1038/s41374-018-0150-4.
Longfei Dai 1 2 3,  Wendi Hu 1 2 3,  Zhenjie Yang 1 2 3,  Diyu Chen 1 2 3,  Bin He 1 2 3,  Yunhao Chen 1 2 3,  Lin Zhou 2 3 4,  Haiyang Xie 2 3 4,  Jian Wu 5 6 7,  Shusen Zheng 8 9 10 11
Affiliations

Affiliations

  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China.
  • 2 Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China.
  • 3 Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China.
  • 4 Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, 310000, China.
  • 5 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China. [email protected].
  • 6 Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China. [email protected].
  • 7 Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, 310000, China. [email protected].
  • 8 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, China. [email protected].
  • 9 Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China. [email protected].
  • 10 Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, 310003, China. [email protected].
  • 11 Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, Hangzhou, 310000, China. [email protected].
PMID: 30664713 DOI: 10.1038/s41374-018-0150-4
Abstract

Homeobox B7 (HOXB7) protein is reported to be aberrantly expressed in a variety of cancers and to play an important role in multiple cellular processes. However, the specific mechanism by which HOXB7 promotes the malignant progression of intrahepatic cholangiocarcinoma (ICC) remains unclear. Therefore, we used quantitative real-time polymerase chain reaction (PCR) to detect the expression level of HOXB7 in 38 paired ICC tissue samples. Additionally, to assess correlation between HOXB7 and ICC prognosis, we performed immunohistochemistry (IHC) using 122 ICC tissues to detect HOXB7 expression. Cell Counting Kit-8 (CCK-8) and colony formation assays were employed to assess ICC cell proliferation, and Transwell assays were performed to estimate the invasion and migration abilities of ICC cells. The capillary tube formation assay was applied to explore the angiogenic effects of HOXB7. A xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth and lung metastasis. The results showed higher expression of HOXB7 in ICC tissues than in noncancerous tissues, and this increased expression was significantly associated with a poor prognosis. In addition, HOXB7 overexpression enhanced capillary tube formation, invasion and migration of ICC cells in vitro, whereas HOXB7 knockdown produced the opposite results in vitro. Moreover, the role of HOXB7 in promoting tumor growth and metastasis was verified in vivo. Further investigation revealed that the expression levels of MMP2, MMP9, VEGFa, and IL8 were elevated by HOXB7 and that the ERK pathway was activated. Our results demonstrate the prognostic value of HOXB7 and its role in metastasis and angiogenesis in ICC. HOXB7 upregulated MMP2, MMP9, VEGFa, and IL8 expression via the ERK pathway to accelerate the malignant progression of ICC.

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Products
  • Cat. No.
    Product Name
    Description
    Target
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  • HY-50846
    99.27%, ERK1/2 Inhibitor
    ERK