The Sweet Shadow of Fructose "Triggering Cancer Metastasis"

Fructose - KHK-A - Revealing a New Pathway Leading to Gene Regulation

On the 13th, with cool early autumn weather, a honeybee is collecting nectar in the cosmos field at Deulkkotmaru, Olympic Park, Songpa-gu, Seoul. Photo by Hyunmin Kim kimhyun81@

[Asia Economy Reporter Junho Hwang] The hidden shadow of fructose, a naturally occurring sweet substance found in fruits and honey, has been uncovered by Korean researchers. Animal experiments confirmed that excessive consumption of fructose can promote cancer metastasis. As the consumption of instant foods increases, leading to higher fructose intake, this study is expected to raise awareness about fructose.

According to the Korea Research Foundation on the 15th, a research team led by Professor Jongwan Park of Seoul National University College of Medicine revealed that the expression of genes suppressed by fructose triggers cancer metastasis using breast cancer cells and a breast cancer xenograft mouse model. The related research findings were recently published in the international journal Nature Communications.

The Secret of the Enzyme That Does Not Metabolize Fructose

The Role of Fructose in Cancer Metastasis Confirmed through a Mouse Model Transplanted with Cancer Cells Expressing KHK-A

This study is significant in that it elucidates the specific mechanism by which fructose intake affects cancer metastasis. Until now, excessive fructose consumption was only known to be associated with metabolic diseases or the onset and progression of various cancers such as breast, colon, and lung cancer. Fructose is used as a sweetener that provides sweetness but is a cause of several metabolic diseases including obesity, fatty liver, and diabetes. Sugar is also broken down into fructose in the body.

The research team focused on ketohexokinase-A (KHK-A), a fructose-phosphorylating enzyme structurally very similar to ketohexokinase-C (KHK-C), which metabolizes fructose but does not metabolize fructose itself. KHK-C is distributed only in metabolic organs such as the liver, kidney, and small intestine, whereas KHK-A, which cannot digest fructose, is distributed in all organs, and its role had not been clarified, drawing attention.

Cancer Metastasis in Mice Excessively Consuming Fructose

The 'Fructose ? KHK-A ? YWHAH' signaling pathway identified in this study.

The research team uncovered the secret of KHK-A through mice with breast cancer. They confirmed that cancer metastasis was vigorous in mice transplanted with cancer cells that continuously produced KHK-A among those that consumed fructose.

The team also revealed the process of cancer metastasis. Fructose moves KHK-A from the cytoplasm into the nucleus, where KHK-A phosphorylates the nuclear protein YWHAH. The phosphorylated YWHAH binds to and activates SLUG, a transcription factor. SLUG then binds to the promoter of the tumor suppressor gene CDH1, suppressing its transcription, which results in enhanced cancer cell mobility and subsequent metastasis.

To explain this complex process simply, KHK-A modifies proteins in the cell nucleus, ultimately preventing tumor suppressor genes from functioning properly, allowing cancer cells to spread throughout the body. Cancer metastasis begins when some rapidly proliferating cancer cells detach from the existing tumor tissue and enter blood vessels, a process initiated by the reduction of adhesion proteins that connect cells, according to the study.

The research team reported that in a mouse model possessing a mutant protein (YWHAH) that does not undergo protein modification by KHK-A, cancer metastasis did not occur despite excessive fructose intake.

Need for Clinical Trials on Actual Cancer Patients

Professor Jongwan Park, Ji-young Kim, Integrated Master's and Doctoral Program Student at Seoul National University, Jeongmin Kang, Postdoctoral Researcher at Stanford University

The research team anticipates that clinical studies will be necessary to examine the effects of fructose on the human body, especially on cancer patients.

The team explained, "This research result was obtained by applying about 15% fructose mixture to a mouse model," adding, "To determine the appropriate level of fructose intake for actual cancer patients using fructose-containing diets during nutritional supplementation, clinical trials involving humans are needed."

They continued, "This study provides hints on what kinds of foods should be recommended to patients to halt cancer progression," and added, "It is probably best to avoid excessively sweet foods." Furthermore, "This study identified that KHK-A phosphorylates proteins, and based on these results, it is expected that new therapeutics to stop cancer progression can be developed."

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