The CD133+CXCR4+ Colorectal Tumor Cells Promote Colorectal Cancer Progression by PI3K/AKT Signaling

J Interferon Cytokine Res. 2022 May;42(5):195-202. doi: 10.1089/jir.2021.0207. Epub 2022 Apr 4.

Abstract

Colorectal cancer (CRC) is one of the most common cancers in the world. Due to its preferential metastasis to the liver, CRC has become one of the leading causes of cancer-related deaths worldwide. There has evidence showing that a variety of subpopulations exist among cancer cells, which play an important role in liver metastasis. Growing evidence suggests that CD133 and C-X-C chemokine receptor type 4 (CXCR-4) are thought to contribute to cancer progression and metastasis. However, it has not been fully characterized in CRC. Here, we found that the expression of CD133 and CXCR4 in metastatic liver cancer tissues was higher than that of the primary tumor tissue and paratumor tissue. Furthermore, CD133+CXCR4+ cells were found to contribute to colorectal carcinogenesis and liver metastasis in vitro and in vivo. Moreover, CXCR4 blocked significantly inhibited the CD133+CXCR4+ cells metastatic to the liver in a mouse model. We also showed that CD133+CXCR4+ induced significant phosphorylation of PI3K/AKT. In conclusion, our data demonstrate that CD133+CXCR4+ cell subsets play an important role in the development and progression of colon cancer.

Keywords: CD133; CXCR4; colorectal cancer; liver metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen / immunology
  • Animals
  • Colorectal Neoplasms*
  • Liver Neoplasms* / metabolism
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, CXCR4 / metabolism
  • Signal Transduction

Substances

  • AC133 Antigen
  • Receptors, CXCR4
  • Proto-Oncogene Proteins c-akt