Open Access

A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition

  • Authors:
    • Hyung-Hoon Oh
    • Young-Lan Park
    • Sun-Young Park
    • Young-Eun Joo
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  • Published online on: March 1, 2023     https://doi.org/10.3892/ijo.2023.5498
  • Article Number: 50
  • Copyright: © Oh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

A disintegrin and metalloprotease 12 (ADAM12) and epithelial‑mesenchymal transition (EMT) are linked in the metastasis of various types of cancer. The present study aimed to assess the ability of ADAM12 to induce EMT and its potential as a therapeutic target for colorectal cancer (CRC). ADAM12 expression in CRC cell lines, CRC tissues and a mouse model of peritoneal metastasis was assessed. The effect of ADAM12 on CRC EMT and metastasis was investigated using ADAM12‑pcDNA6‑myc and ADAM12‑pGFP‑C‑shLenti constructs. ADAM12 overexpression enhanced the proliferation, migration, invasion and EMT of CRC cells. The phosphorylation levels of factors associated with the PI3K/Akt pathway were also increased by ADAM12 overexpression. The knockdown of ADAM12 reversed these effects. ADAM12 expression and the loss of E‑cadherin expression were significantly associated with poorer survival compared with other expression statuses of both proteins. In a mouse model of peritoneal metastasis, overexpression of ADAM12 induced increased tumor weight and peritoneal carcinomatosis index compared with that in the negative control group. Conversely, knockdown of ADAM12 reversed these effects. Furthermore, E‑cadherin expression was significantly decreased by overexpression of ADAM12 compared with in the negative control group. By contrast, E‑cadherin expression was increased by knockdown of ADAM12 compared with in the negative control group. ADAM12 overexpression contributed to CRC metastasis by regulating EMT. In addition, in the mouse model of peritoneal metastasis, ADAM12 knockdown exhibited strong anti‑metastatic action. Consequently, ADAM12 may be considered a therapeutic target for CRC metastasis.
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April-2023
Volume 62 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Oh H, Park Y, Park S and Joo Y: A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition. Int J Oncol 62: 50, 2023
APA
Oh, H., Park, Y., Park, S., & Joo, Y. (2023). A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition. International Journal of Oncology, 62, 50. https://doi.org/10.3892/ijo.2023.5498
MLA
Oh, H., Park, Y., Park, S., Joo, Y."A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition". International Journal of Oncology 62.4 (2023): 50.
Chicago
Oh, H., Park, Y., Park, S., Joo, Y."A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition". International Journal of Oncology 62, no. 4 (2023): 50. https://doi.org/10.3892/ijo.2023.5498