Metastatic melanoma is a highly aggressive skin cancer whose incidence is on the rise at an alarming rate. Research has revealed that metastatic tumor cells share similar signaling pathways with embryonic stem cells to sustain plasticity and growth. However, major regulators of these pathways are often missing in tumor cells, thus allowing uncontrolled tumor growth and spreading to occur.
During early vertebrate development, Nodal, an embryonic growth factor that governs the growth, pattern and position of tissues, is critical for normal maturation. Nodal plays a significant role in maintaining the pluripotency of embryonic stem cells, meaning the ability of stem cells to differentiate into any of the three germ layers that comprise the body.
The recent discovery of Nodal's re-expression in several aggressive and metastatic cancers has highlighted its critical role in self-renewal and maintenance of the stem cell-like characteristics of tumor cells such as melanoma. However, the signaling pathway receptors utilized by melanoma cells to propagate Nodal's effect remain(s) mostly anecdotal and unexplored.
The laboratory of Mary J.C. Hendrix, PhD made the novel discovery that embryonic stem cells and metastatic melanoma cells share a similar repertoire of receptors known as Type I serine/threonine kinase(s), but diverge in their Type II receptor expression.
Further testing indicated that metastatic melanoma cells and embryonic stem cells use different receptors for Nodal signal transduction. These findings reveal the divergence in Nodal signaling between embryonic stem cells and metastatic melanoma that can impact new therapeutic strategies targeting the re-emergence of embryonic pathways in cancer.
This work is published in the International Journal of Cancer. Mary J.C. Hendrix, PhD points out: "Nodal-expressing tumor cells don't respond favorably to conventional therapies, supporting the premise that a combinatorial approach to targeting Nodal subpopulations within tumors, along with a front-line therapy, would constitute a more rational approach for treating aggressive cancer".
Zhila Khalkhali-Ellis, PhD, senior research scientist in the Hendrix laboratory and the lead author says: "Our discoveries are important for advanced stage aggressive melanoma. Given that limited therapeutic options are currently available for this cancer, we have the opportunity to investigate whether the receptors can be modulated so that the signaling molecule can be neutralized to decrease aggressive behavior." The research was supported by the National Institutes of Health.
Zhila Khalkhali-Ellis, PhD is Research Associate Professor of Pediatrics at Northwestern University Feinberg School of Medicine; and a member of the Cancer Biology and Epigenomics Program of Stanley Manne Children's Research Institute, affiliated with Ann & Robert H. Lurie Children's Hospital of Chicago.
Mary J.C. Hendrix, PhD is President & Scientific Director of Manne Research Institute; Children's Research Fund Professor; William G. Swartchild, Jr. Distinguished Research Professor at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The research team includes members of the Department of Pediatrics at Northwestern University Feinberg School of Medicine, Chicago, Illinois and the Department of Biochemistry at the University of Texas Health Sciences Center, San Antonio, Texas.
Full citation: Khalkhali-Ellis Z, Kirschmann DA, Seftor EA, Gilgur A, Bodenstine TM, Hinck AP, Hendrix MJC. Divergence(s) in Nodal Signaling Between Aggressive Melanoma and Embryonic Stem Cells. International Journal of Cancer. Available online September 9, 2014.
Stanley Manne Children's Research Institute is the research arm of Ann & Robert H. Lurie Children's Hospital of Chicago, the pediatric teaching hospital for Northwestern University Feinberg School of Medicine. The research institute is also one of the interdisciplinary research centers and institutes of the Feinberg School, where principal investigators who are part of the research institute are full-time faculty members.
225 E. Chicago Ave., Box 205
Chicago, IL 60611
Affiliated with Northwestern University Feinberg School of Medicine
Peggy Murphy | Eurek Alert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences