Open Access

Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer

  • Authors:
    • Maha Abdulla
    • Thamer Bin Traiki
    • Mansoor-Ali Vaali‑Mohammed
    • Mohammad S. El‑Wetidy
    • Noura Alhassan
    • Khayal Al‑Khayal
    • Ahmed Zubaidi
    • Omar Al‑Obeed
    • Rehan Ahmad
  • View Affiliations

  • Published online on: January 21, 2022     https://doi.org/10.3892/ijo.2022.5312
  • Article Number: 22
  • Copyright: © Abdulla et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

With >1.85 million cases and 850,000 deaths annually, colorectal cancer (CRC) is the third most common cancer detected globally. CRC is an aggressive malignancy with metastasis and, in spite of advances in improved treatment regimen, distant disease failure rates remain disappointingly high. Mucin‑like 1 (MUCL1) is a small glycoprotein highly expressed mainly in breast cancer. The involvement of the MUCL1 protein in CRC progression and the underlying mechanism have been largely unknown. The aim of the present study was to investigate the MUCL1 expression profile and its functional significance in CRC. The Cancer Genome Atlas dataset revealed that MUCL1 expression was higher in colorectal tumor compared with normal tissues. MUCL1 was also revealed to be expressed in human CRC cell lines. The results demonstrated that MUCL1 promoted cell proliferation and colony formation, confirming its oncogenic potential. Silencing MUCL1 with short interfering RNA inhibited the protein expression of Bcl2 family proteins, such as Bcl2 and BclxL. Targeting MUCL1 resulted in significant inhibition in cell invasive and migratory behavior of HT‑29 and SW620 cells. In addition, the expression of E‑cadherin increased whereas the expression of vimentin decreased in MUCL1‑silenced cells, confirming inhibition of epithelial‑mesenchymal transition (EMT) process. Thus, it was revealed that MUCL1 plays a notable role in cell invasion and migration by inhibiting EMT in CRC. Mechanistically, MUCL1 drives β‑catenin activation by Ser‑552 phosphorylation, nuclear accumulation and transcriptional activation. Targeting MUCL1 increases the drug sensitivity of CRC cells towards irinotecan. These findings thus demonstrated that MUCL1 acts as a modifier of other pathways that play an important role in CRC progression and MUCL1 was identified as a potential target for CRC therapeutics.
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March-2022
Volume 60 Issue 3

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Spandidos Publications style
Abdulla M, Traiki TB, Vaali‑Mohammed M, El‑Wetidy MS, Alhassan N, Al‑Khayal K, Zubaidi A, Al‑Obeed O and Ahmad R: Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer. Int J Oncol 60: 22, 2022
APA
Abdulla, M., Traiki, T.B., Vaali‑Mohammed, M., El‑Wetidy, M.S., Alhassan, N., Al‑Khayal, K. ... Ahmad, R. (2022). Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer. International Journal of Oncology, 60, 22. https://doi.org/10.3892/ijo.2022.5312
MLA
Abdulla, M., Traiki, T. B., Vaali‑Mohammed, M., El‑Wetidy, M. S., Alhassan, N., Al‑Khayal, K., Zubaidi, A., Al‑Obeed, O., Ahmad, R."Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer". International Journal of Oncology 60.3 (2022): 22.
Chicago
Abdulla, M., Traiki, T. B., Vaali‑Mohammed, M., El‑Wetidy, M. S., Alhassan, N., Al‑Khayal, K., Zubaidi, A., Al‑Obeed, O., Ahmad, R."Targeting MUCL1 protein inhibits cell proliferation and EMT by deregulating β‑catenin and increases irinotecan sensitivity in colorectal cancer". International Journal of Oncology 60, no. 3 (2022): 22. https://doi.org/10.3892/ijo.2022.5312