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Hidden Mechanism for the Suppression of Colon Cancer Identified

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Posted April 18, 2014

Korean researchers have successfully identified the cancer inhibitory mechanism of the colon tissue. The discovery of the inherent defense mechanism of the colon tissues is expected to provide understanding of the cause of colorectal cancer.

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Crypt: Epithelium, consisting of approximately 2,000 cells, forms a colon surface in the shape of a cave.

The research was led by Kwang-Hyun Cho, a professor of Bio and Brain Engineering at KAIST (corresponding author) and participated by Dr. Jehun Song (the first author), as well as Dr. Owen Sansom, David Huels, and Rachel Ridgway from the Beatson Institute for Cancer Research in the UK and Dr. Walter Kolch from Conway Institute in Ireland.

The research was funded by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea, and its results were published in the 28th March online edition of Cell Reports under the title of “The APC network regulates the removal of mutated cells from colonic crypts.”

The organism can repair damaged tissues by itself, but genetic mutations, which may cause cancer, can occur in the process of cell division s for the repair. The rapid cell division s and toxic substances from the digestive process cause a problem especially in colon crypt that has a high probability for genetic mutation.

The research team was able to find out that the colon tissues prevent cancer by rapidly discharging carcinogenic cells with genetic mutations from the colon crypt durin ga frequent tissue repair process.

This defense mechanism, which inhibits abnormal cell division s by reducing the time mutated cells reside in the crypt, is inherent in the colon.

Extensive mathematical simulation results show that the mutated cells with enhanced Wnt signaling acquire increased adhesion in comparison to the normal cells, which therefore move rapidly toward the upper part of the crypt and are discharged more easily.

Wnt Signaling: A signal transduction pathway involved in the proliferation and differentiation of cells that are particularly important for the embryonic development and management of adult tissue homeostasis.

Wnt Signaling: A signal transduction pathway involved in the proliferation and differentiation of cells that are particularly important for the embryonic development and management of adult tissue homeostasis.

If beta-catenine, the key factor in Wnt signal transduction pathway, is not degraded due to genetic mutation, the accumulated beta-catenine activates cell proliferation and increases cell adhesion. The special environment of crypt tissue and the tendency of the cells with similar adhesion to aggregate will therefore discharge the mutated cell, hence maintaining the tissue homeostasis.

In vivo experiment with a mouse model confirms the simulation results that, in the case of abnormal crypt, the cells with high proliferation in fact move slower.

Professor Cho said, “This research has identified that multicellular organism is exquisitely designed to maintain the tissue homeostasis despite abnormal cell mutation. This also proves the systems biology research, which is a convergence of information technology and bio-technology , can discover hidden mechanisms behind complex biological phenomena.”

Source: KAIST

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