The Secret of 'Colon Cancer Metastasis' Caused by Cholesterol

Discovery of Key Regulatory Protein Driving Malignant Progression of Colorectal Cancer
Expected Development of Anti-Cancer Drugs to Inhibit Colorectal Cancer Metastasis and Biomarkers for Diagnosis

This is a schematic diagram illustrating the acceleration of colorectal cancer metastasis by cholesterol. In the early stages of colorectal cancer, SQLE is highly expressed and cholesterol levels are low. However, the overexpressed SQLE binds to GSK3β and p53, increasing cholesterol synthesis. Subsequently, when a large amount of cholesterol accumulates within colorectal cancer cells, SQLE is degraded and decreases. As a result, the SQLE-GSK3β-p53 complex dissociates, activating the Wnt pathway and promoting colorectal cancer metastasis.

[Asia Economy Reporter Junho Hwang] Domestic researchers have elucidated the mechanism by which cholesterol promotes the progression and malignancy of colorectal cancer. This discovery is expected to contribute to the development of new cancer treatments targeting colorectal cancer malignancy and the creation of markers for prognosis assessment.

Cholesterol Makes Colorectal Cancer Malignant

Decrease in SQLE and E-cadherin expression levels in metastatic cancer compared to primary colorectal cancer

The research team led by Dr. Namsoon Kim from the Rare and Intractable Disease Research Center at the Korea Research Institute of Bioscience and Biotechnology recently published their findings on the process by which cholesterol intake from Western dietary habits leads to colorectal cancer progression in the international journal of gastroenterology, Gastroenterology, on the 15th.

The team revealed that cholesterol accumulated in colorectal cancer cells causes the degradation of a key cholesterol synthesis enzyme, which in turn activates major cancer metastasis pathways, inducing colorectal cancer metastasis.

The researchers confirmed that as colorectal cancer metastasis progresses, the expression of the receptor (LDLR) that delivers blood cholesterol to cancer cells increases, while the expression of the synthesis enzyme (SQLE) protein decreases. They also found that administering cholesterol or suppressing SQLE expression leads to metastasis of colorectal cancer cells to tissues such as the lungs and liver. The team explained that this is because the activation of major metastasis pathways generates cancer stem cells, which simultaneously promotes colorectal cancer cell metastasis and increases cancer cell survival.

In summary, cholesterol accumulates inside colorectal cancer cells through highly expressed LDLR in high-cholesterol colorectal cancer patients, leading to the degradation of SQLE, activation of major cancer metastasis pathways, and thus promoting the progression and metastasis of colorectal cancer.

Potential for New Drug Development for Colorectal Cancer Treatment

Increased metastasis of colon cancer cells by cholesterol treatment or SQLE expression suppression (A, B), increase in circulating cancer stem cells and decrease in SQLE expression (C)

The research team identified the SQLE protein as a key regulator of colorectal cancer malignancy, marking the first molecular mechanism elucidating the clinically observed correlation between cholesterol and colorectal cancer metastasis.

Dr. Namsoon Kim, the principal investigator, stated, "This research outcome reveals that SQLE protein is a critical factor for effectively diagnosing and treating colorectal cancer metastasis caused by excessive cholesterol accumulation. By developing metastasis-inhibiting therapeutic agents targeting SQLE and diagnostic systems for predicting metastasis and recurrence based on the findings of this study, we can provide diagnostic and treatment guidelines for colorectal cancer patients."

Meanwhile, colorectal cancer is the third most common cancer worldwide, and the primary cause of death from colorectal cancer is metastasis. The metastasis rate of colorectal cancer in Koreans is approximately 35%, which is very high. Cholesterol is a major component of cell membranes and a precursor substance to steroid hormones. However, since the mechanism related to cancer metastasis had not been elucidated, the development of cholesterol-based anti-cancer drugs to inhibit colorectal cancer metastasis or markers to predict metastasis and recurrence of colorectal cancer had been difficult.

This content was produced with the assistance of AI translation services.