Role of Tetraspanin-6 in bowel cancer

Aqsa, Jamia Millia Islamia

Bowel cancer is also known as colorectal cancer. The colon and rectum are the last part of our large intestine, where this cancer occurs. At first, this cancer tumour appears as a small clump of calls celled polyps. These polyps are non-cancerous but can turn cancerous if not treated on time. But the problem is that these polyps do not produce any symptoms. So their prior detection is not possible. It only gives manifestation once it becomes cancerous. The symptoms include:

• weakness and fatigue
• weight loss
• a feeling that your bowl didn’t get emptied
• abdominal pain
• rectal bleeding
• diarrhoea or constipation

The treatments available for bowel cancer are Chemotherapy, radiation therapy, targeted drug therapy, immunotherapy, surgery, etc. 

Drug therapy for Bowel cancer:

In colorectal cancer, there is a rapid change in transcriptional activities leading to multiple gene expressions. The new finding at the University of Birmingham reveals a new pathway. This pathway resists the function of a specific drug used for bowel cancer. The researchers studied the tumour sample of 184 patients. These patients participated in the COIN trial, which aimed at finding a possible solution for patients in their advanced stage of Bowel cancer. The drugs called anti-EGFR inhibitors are effective for bowel cancer for about 60%. But this drug does not work most of the time or becomes ineffective. The study revealed a pathway involving a protein called tetraspanin 6. This pathway becomes inactive in patients with bowel cancer and, in turn, makes the anti-EFGR drugs less effective.

Role of Tetraspanin-6:

Tetraspanin-6 is a protein that belongs to the tetraspanin family and acts as a tumour suppressor in colorectal cancer. It mainly affects the epidermal growth factor receptor (EGFR)–based signalling axis by reducing it. The expression of tetraspanin-6 protein often gets decreased in bowel cancer. Lower production of this protein results in the ineffectiveness of EGFR-targeted therapy. These results concluded tetraspanin-6 is a regulator of bowel cancer development and a biomarker for EGFR-targeted therapies.

The expression of proteins belonging to the tetraspanin family gets dysregulated in bowel cancer. Studies also revealed that the mRNA levels of tetraspanins get altered in bowel cancer. Tetraspanins usually affect tumour cell behaviour such as cell proliferation, cell migration, and invasion through some signalling pathways. Tetraspanin-6 protein remains involved in bowel cancer development. It helps in regulating the epidermal growth factor receptor (EGFR) pathway. This EGFR signalling pathway is essential as it helps in tumour growth and progression. Therapies targeting EGFR-pathway have proved to be a promising solution in colorectal cancer patients. But the problem arises as some tumours show resistance to anti-EGFR drugs. This may be due to mutations in the EGFR-dependent pathway or activation of an alternate pathway.

Outcomes

The deletion of the gene coding for tetraspanin-6 resulted in increased tumour size and the formation of adenoma. Studies also concluded that the expression of tetraspanin-6 in bowel cancer leads to better responses to EGFR-targeted therapeutic drugs such as Cetuximab. Patients with active tetraspanin-6 protein showed a better response to Cetuximab. And patients with a lower level of protein did not show a positive result to the drug. 

Also read: What factors increase the risk of breakthrough infection?

Reference: Andrijes, Regina, et al. “Tetraspanin 6 Is a Regulator of Carcinogenesis in Colorectal Cancer.” Proceedings of the National Academy of Sciences, vol. 118, no. 39, Sept. 2021. www.pnas.org, https://doi.org/10.1073/pnas.2011411118.

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