Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discovered a new targetable vulnerability in breast cancer cells

29.03.2019

Uncontrolled growth of cancer arises from the imbalanced regulation of cell division and programmed cell death. To stimulate the growth, cancer cells can induce multiple signaling receptors; including FGFR4 receptor tyrosine kinase, for which the cancer promoting signaling routes have remained incompletely understood.

In breast cancer, FGFR4 is especially overexpressed in the subset, where cell proliferation is driven by another related signaling receptor, HER2. Targeted therapies against HER2 are in use to effectively treat the patients with HER2-positive breast cancer.


New study reveals that FGFR4 phosphorylates the essential proteins (MST1/2) of Hippo tumor suppressor pathway preventing their activation and induction of programmed cell death in breast cancer cells. Cell death program can be reactivated by blocking FGFR4 function with a specific inhibitor. These findings suggest new options for eradicating cancer cells with excessive FGFR4 expression.

Credit: M Varjosalo & Lehti Group

Because in these tumors excessive FGFR4 expression associates with poor patient survival, combinatorial drug targeting of FGFR4 could prevent the spread of improve treatment efficacy for those patients whose tumors spread aggressively despite HER2 targeting.

Based on this idea, the new study led by Associate Professor Kaisa Lehti first comprehensively elucidated the functions of FGFR4 by screening thousands of candidate proteins that can be modified by FGFR4 mediated phosphorylation.

"Unexpectedly, we discovered that FGFR4 efficiently phosphorylates several essential proteins of the Hippo tumor suppressor pathway", Lehti tells. As the name suggests, Hippo pathway suppresses uncontrolled growth, and disturbances of the Hippo pathway signaling contribute to outgrowth of the tumors.

Biochemical studies on breast cancer cells revealed that, by phosphorylating MST1/2 Hippo kinases, FGFR4 not only regulated growth, but also prevented the induction of programmed cell death. In these cancers driven by both HER2 and FGFR4 signaling, the cells were forced to actively suppress programmed cell death pathways via the herein identified mechanism to survive and grow.

Although such complex cancer cell signaling mechanisms may seem peculiar and almost invincible, they provide also great chances for drug targeting. FGFR4 receptor has distinct structural features allowing for specific targeting with drugs, and several compounds of this type are already in use for basic research and clinical trials.

In this study, the researchers utilized a comprehensive oncology drug testing, which revealed that a treatment combining an FGFR4 targeting drug either with HER2 targeted therapy or modulators of the cell intrinsic death program efficiently reduced breast cancer cell viability.

"This clearly reveals a co-targetable vulnerability of cancer cell signaling, and these promising results warrant future studies to investigate the potential of FGFR4 targeting to combat HER2 positive breast cancer or other cancer types where FGFR4 is overexpressed", Lehti summarizes.

The results were published in Cell Death and Differentiation journal.

###

This study was funded by the Academy of Finland, University of Helsinki, Cancer Foundation Finland, K. Albin Johansson Foundation, Sigrid Jusélius Foundation, Karolinska Institutet, KI Strategic Research Program in Cancer (StratCan-KICancer), Swedish Cancer Society, Swedish Research Council, Knut and Alice Wallenberg Foundation, Science for Life Laboratory, Magnus Ehrnrooth Foundation, Medicinska understödsföreningen Liv och hälsa, and the The Finnish Society of Sciences and Letters.

Media Contact

Dr. Kaisa Lehti
kaisa.lehti@helsinki.fi
358-503-230-267

 @helsinkiuni

http://www.helsinki.fi/university/ 

Dr. Kaisa Lehti | EurekAlert!
Further information:
https://www.helsinki.fi/en/news/health-news/researchers-discovered-a-new-targetable-vulnerability-in-breast-cancer-cells
http://dx.doi.org/10.1038/s41418-019-0321-x

More articles from Life Sciences:

nachricht New eDNA technology used to quickly assess coral reefs
18.04.2019 | University of Hawaii at Manoa

nachricht New automated biological-sample analysis systems to accelerate disease detection
18.04.2019 | Polytechnique Montréal

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

Im Focus: Researchers 3D print metamaterials with novel optical properties

Engineers create novel optical devices, including a moth eye-inspired omnidirectional microwave antenna

A team of engineers at Tufts University has developed a series of 3D printed metamaterials with unique microwave or optical properties that go beyond what is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>