Researchers discover a novel role of protein in important pathways that lead to cancer malignancy

August 31, 2018, Shinshu University
High expression of FABP5 promotes fatty acid metabolism through lipolysis and de novo fatty acid synthesis in prostate and breast cancer cells. Activation of PKC and increase in ROS levels by FABP5 induce NF-κB and expression of its target genes involved in cancer development. Credit: Hiroshi Fujii Ph.D., the Institute for Biomedical Sciences, Shinshu University

Japanese researchers have revealed for the first time that a specific protein plays a critical role in the development and metastasis of highly aggressive prostate and breast cancer cells.

The study reports that large amounts of the fatty acid-binding protein 5 (FABP5), a kind of transport protein for fatty acids, promotes processes associated with aggressiveness such as cell growth, invasiveness, survival and inflammation in prostate and breast . The researchers point out that a better understanding of the molecular pathways of specific cancers is a step in the direction of finding more effective therapeutic targets.

Altered is thought to be a hallmark of cancer. It is known that cancer cells exhibit significantly increased demands for energy, mass, and large molecules to keep multiplying and spreading as part of their metastatic behavior. It has also recently been revealed that alterations of play pivotal roles in cancer development and metastasis. Furthermore, although cancer cells with high levels of (LDs) are more resistant to chemotherapy, the molecular mechanisms behind this remain unclear. Therefore, it is very important to identify the critical genes involved in metabolic reprogramming and regulation of LDs formation during carcinogenesis to develop novel diagnostic tools and treatments for cancers.

Professor Hiroshi Fujii, Vice-Director of the Institute for Biomedical Sciences at Shinshu University and the project lead, adds that he and his team have "demonstrated that there is a specific pathway behind FABP5 inflammation as well as production of immune substances in specific cancer cells. Therefore, FABP5 could be expected to be a target for development of therapeutic reagents and/or a biomarker for prostate and breast cancers in the future."

The process of lipid metabolism includes events such as lipogenesis, lipid storage as well as degradation. Any irregularities in lipid metabolism in cancer cells are frequently detected and used as an indicator for tumor malignancy. Fatty acids, in particular, are involved in several aspects of the formation of tumors.

The research team used several methods to reveal how FABP5 expression levels affect the genes that are involved in crucial processes of aggressive prostate and .

The authors also add that, "Understanding the alterations of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for treatment of cancer. For example, cholesterol ester and (FAs) are required as an energy source and for production of cellular signaling molecules and the formation of membrane components during cancer cell proliferation and metastasis."

The study was published in BBA—Molecular and Cell Biology of Lipids in June 2018. The researchers used standard molecular biology methods to obtain their results and show that certain genes are upregulated (or "turned on") by FABP5 expression. These genes are changed in several crucial processes during multiplication and division of aggressive cancer cells.

The authors state that while in the current study they have revealed that FABP5 might regulate lipid quality and/or quantity, but that the details of molecular mechanisms of metabolic reprogramming of lipids mediated by FABP5 are yet to be fully understood. Professor Fujii says, "Studies on analyses of lipid droplet contents should be needed to reveal alterations of profiling induced by FABP5 in cancer cells in the future."

Explore further: Ovarian cancer cells hoard iron to fuel growth

More information: Shogo Senga et al, Fatty acid-binding protein 5 (FABP5) promotes lipolysis of lipid droplets, de novo fatty acid (FA) synthesis and activation of nuclear factor-kappa B (NF-κB) signaling in cancer cells, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (2018). DOI: 10.1016/j.bbalip.2018.06.010

Related Stories

Ovarian cancer cells hoard iron to fuel growth

August 15, 2018
An unexpected link between iron and fatty acids may be juicing the metabolism of ovarian cancer cells, report UConn Health researchers in the July 1 issue of OMICS: A Journal of Integrative Biology. The findings could suggest ...

Research identifies new breast cancer therapeutic target

July 18, 2018
Research led by Suresh Alahari, Ph.D., Professor of Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine, has shown for the first time that a tiny piece of RNA deregulates energy metabolism, an ...

Discovery of a new metabolic pathway of a known lipid has implications in cancer, obesity

March 10, 2017
A collaborative Stony Brook University research team has discovered a novel metabolic pathway of the lipid ceramide, which is involved in cell death. The finding illustrates that ceramide is stored in lipid droplets, a step ...

Study finds how fat tissue shunts energy to tumors

April 9, 2018
Obesity is the second-leading preventable cause of cancer and represents one of the greatest threats to global human health. But it has not been clear exactly how whole-body metabolism affects tumor formation. In particular, ...

Study highlights possible Achilles' heel in key immune memory cells

March 9, 2017
The capacity for memory isn't exclusive to the brain. The immune system, with its sprawling network of diverse cell types, can recall the pathogens it meets, helping it to swiftly neutralize those intruders upon future encounters.

Recommended for you

Pancreatic cancer's addiction could be its end

November 13, 2018
Cancer cells are often described as cells "gone bad" or "renegade." New research reveals that in some of the deadliest cases of pancreatic cancer, these rebellious cells have an unexpected addiction. Now, scientists are investigating ...

Cognitive decline—radiation—brain tumor prevented by temporarily shutting down immune response

November 13, 2018
Treating brain tumors comes at a steep cost, especially for children. More than half of patients who endure radiation therapy for these tumors experience irreversible cognitive decline, a side-effect that has particularly ...

Study finds promising therapeutic target for aggressive type of breast cancer

November 13, 2018
A new Nature Communications study led by University of Kentucky Markey Cancer Center researchers suggests that an enzyme known as Prolyl 4-hydroxylase subunit alpha-1 (P4HA1) is a potential therapeutic target for triple negative ...

Obesity both feeds tumors and helps immunotherapy kill cancer

November 12, 2018
A groundbreaking new study by UC Davis researchers has uncovered why obesity both fuels cancer growth and allows blockbuster new immunotherapies to work better against those same tumors.

Spread of deadly eye cancer halted in cells and animals

November 12, 2018
By comparing genetic sequences in the eye tumors of children whose cancers spread with tumors that didn't spread, Johns Hopkins Medicine researchers report new evidence that a domino effect in cells is responsible for the ...

Cancer stem cells get energy from protein, and it's proving to be their Achilles' heel

November 12, 2018
Think of energy metabolism like a party popper: Ripping something apart releases a bang. Most of your cells rip apart sugar to release the "bang" of energy. Sometimes they rip apart fats, and in a pinch, cells can even metabolize ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.