Mindin serves as a tumour suppressor gene during colon cancer progression through MAPK/ERK signalling pathway in mice

J Cell Mol Med. 2020 Aug;24(15):8391-8404. doi: 10.1111/jcmm.15332. Epub 2020 Jul 2.


Mindin is important in broad spectrum of immune responses. On the other hand, we previously reported that mindin attenuated human colon cancer development by blocking angiogenesis through Egr-1-mediated regulation. However, the mice original mindin directly suppressed the syngenic colorectal cancer (CRC) growth in our recent study and we aimed to further define the role of mindin during CRC development in mice. We established the mouse syngeneic CRC CMT93 and CT26 WT cell lines with stable mindin knock-down or overexpression. These cells were also subcutaneously injected into C57BL/6 and BALB/c mice as well as established a colitis-associated colorectal cancer (CAC) mouse model treated with lentiviral-based overexpression and knocked-down of mindin. Furthermore, we generated mindin knockout mice using a CRISPR-Cas9 system with CAC model. Our data showed that overexpression of mindin suppressed cell proliferation in both of CMT93 and CT26 WT colon cancer cell lines, while the silencing of mindin promoted in vitro cell proliferation via the ERK and c-Fos pathways and cell cycle control. Moreover, the overexpression of mindin significantly suppressed in vivo tumour growth in both the subcutaneous transplantation and the AOM/DSS-induced CAC models. Consistently, the silencing of mindin reversed these in vivo observations. Expectedly, the tumour growth was promoted in the CAC model on mindin-deficient mice. Thus, mindin plays a direct tumour suppressive function during colon cancer progression and suggesting that mindin might be exploited as a therapeutic target for CRC.

Keywords: MAPK/ERK; colorectal cancer; mindin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colitis / genetics
  • Colitis / pathology
  • Colon / pathology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Disease Progression
  • Extracellular Matrix Proteins / genetics*
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • MAP Kinase Signaling System / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • RAW 264.7 Cells
  • Signal Transduction / genetics*


  • Extracellular Matrix Proteins
  • Spon2 protein, mouse