| Autor: |
Abdulla M; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., Traiki TB; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., Vaali-Mohammed MA; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., El-Wetidy MS; College of Medicine Research Center, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., Alhassan N; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., Al-Khayal K; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., Zubaidi A; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., Al-Obeed O; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia., Ahmad R; Colorectal Research Chair, Department of Surgery, King Saud University College of Medicine, Riyadh 11472, Saudi Arabia. |
| Abstrakt: |
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. |
