Research unravels new interactions affecting TGF-beta pathway in humans

December 21, 2015, National University of Singapore
Molecular model showing the novel proposed mechanism for the activation of SMURF2. The C-lobe (in yellow) of the SMURF2 protein interacts with an ubiquitin molecule (in green), which was transferred to SMURF2 by USP15.

Researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) have delineated novel molecular interactions affecting the activity of the TGF-β pathway, a key cancer pathway in humans affecting cancer progression.

In certain settings, the TGF-β can act as an oncogene, enhancing in humans. The activation of this pathway can increase the growth of tumors by promoting cell invasion, activating , and in some cases, promoting the spread of . In recent years, a number of deubiquitinating enzymes have been shown to regulate the TGF-β pathway and may potentially be considered as a new class of drug targets. Studies have shown that the deubiquitinating enzyme USP15 is elevated in glioblastoma, a highly invasive tumor in the brain, as well as breast and ovarian cancers, leading to the over-activation of the TGF-β pathway and increasing cancer risks.

A recent study conducted by Dr Pieter Eichhorn and Dr Prasanna Iyengar from CSI Singapore revealed that the activation of the TGF-β pathway could be influenced by the interactions between USP15 and SMURF2 – enzymes generally involved in degradation of proteins in cells.

"While existing studies have found a number of deubiquitinating enzymes that stabilise the TGF-β receptor, leading to the activation of the TGF-β pathway, the mechanism has not been well studied. Our research found that USP15 could regulate the ability of SMURF2 to add ubiquitin molecules to its targets, resulting in enhanced stability of the TGF-β receptor and downstream pathway activation. Hence, the results of this study point to USP15 as a potential novel therapeutic target for the treatment of cancers with TGF-β hyperactivation," said Dr Eichhorn.

Explore further: The USP15 biological thermostat: A promising novel therapeutic target in cancer

More information: Prasanna Vasudevan Iyengar et al. USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination, Scientific Reports (2015). DOI: 10.1038/srep14733

Related Stories

The USP15 biological thermostat: A promising novel therapeutic target in cancer

February 19, 2012
After years studying the molecular bases of glioblastoma - the most common brain tumor and one of the most aggressive of all cancers, the group led by Dr. Joan Seoane , Director of Translational Research at the Vall d'Hebron ...

Researchers uncover key cancer-promoting gene

January 6, 2015
One of the mysteries in cancer biology is how one protein, TGF-beta, can both stop cancer from forming and encourage its aggressive growth.

Marker may predict breast cancer response to tamoxifen

April 2, 2015
The presence of lower-than-normal amounts of the protein TGFBR2 was associated with breast cancer resistance to treatment with the antiestrogen therapeutic tamoxifen, according to a study published in Cancer Research, a journal ...

Discovery contributes to future treatment of cervical cancer

December 4, 2015
A team of scientists from Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) has uncovered new molecular interactions involved in the development of cervical cancer. Proteins ...

Study discovers genetic pathway impacting the spread of cancer cells

May 3, 2012
In a new study from Lawson Health Research Institute, Dr. Joseph Torchia has identified a new genetic pathway influencing the spread of cancer cells. The discovery of this mechanism could lead to new avenues for treatment.

Recommended for you

Switch discovered to convert blood vessels to blood stem cells in embryonic development

March 20, 2018
A switch has been discovered that instructs blood vessel cells to become blood stem cells during embryonic development in mice. Using single-cell technology, researchers from the Wellcome Sanger Institute in Cambridge and ...

Scientists discover new causes of cellular decline in prematurely aging kids

March 19, 2018
In a recent paper published in Cell Reports, Saint Louis University researchers have uncovered new answers about why cells rapidly age in children with a rare and fatal disease. The data points to cellular replication stress ...

Don't blame adolescent social behavior on hormones

March 19, 2018
Reproductive hormones that develop during puberty are not responsible for changes in social behavior that occur during adolescence, according to the results of a newly published study by a University at Buffalo researcher.

Stem cells treat macular degeneration

March 19, 2018
In July 2015, 86-year-old Douglas Waters developed severe age-related macular degeneration (AMD). He struggled to see things clearly, even when up close.

Measuring neutrophil motility could lead to accurate sepsis diagnosis

March 19, 2018
A microfluidic device developed by Massachusetts General Hospital (MGH) investigators may help solve a significant and persistent challenge in medicine—diagnosing the life-threatening complication of sepsis. In their paper ...

Democratizing science: Researchers make neuroscience experiments easier to share, reproduce

March 16, 2018
Over the past few years, scientists have faced a problem: They often cannot reproduce the results of experiments done by themselves or their peers.


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.