The researchers describe how the two pathways interact to produce their combined effect in a study in the journal Genes and Development that is available online.
Tumor growth occurs upon disruption of the regulation of the cell cycle, the cascade of events that result in the division and duplication of a cell. One critical pathway regulating the cell cycle is the retinoblastoma (Rb) tumor suppressor pathway. The Rb pathway is found to be mutated or functionally inactivated in nearly all human cancers.
Maxim Frolov, UIC associate professor of biochemistry and molecular genetics, models development of human cancer by studying inactivation of Rb in fruit flies. In flies, a deficiency in the Rb pathway alone, he says, surprisingly causes only subtle defects in cell proliferation, but does not result in a full-blown tumor.
"We wanted to understand why,” he said.
One possible explanation was that other regulatory pathways were working together with the Rb pathway. In their previous studies, the researchers had found a pathway called Hippo, which seemed to work with Rb in regulation of cell proliferation.
In the new study, Frolov and his colleagues showed that simultaneously inactivating both pathways led to a marked enhancement of tumor growth. The researchers were able to trace the mechanism responsible for the synergy between these two pathways. They found that inactivation of the Hippo and Rb pathways results in an up-regulaton of a unique set of genes.
“We saw that the genes important to cell proliferation and cell cycle regulation are inappropriately expressed in these cells,” Frolov said. The genes were not up-regulated when either the Rb or Hippo pathway alone was inactivated.
“We found that transcription factors -- proteins that turn genes on and off -- involved in each of the two pathways cooperate in inducing expression of these cell-cycle specific genes, resulting in inappropriate cell proliferation,” he said.
The way Hippo is able to cross-talk with the Rb pathway and disrupt cell-cycle regulation to grow tumors may have important implications for understanding the complexity of mutations in human cancers, Frolov said. The finding suggests that there may be other factors that work with Rb to promote tumor growth.
"We should be looking for more cooperating mutations in human cancers,” he said.
The work is the result of international collaboration between Frolov’s laboratory at UIC and Nuria Lopez-Bigas’s genomics group at the University of Pompeu Fabra in Barcelona, Spain. Brandon Nicolay and Battuya Bayarmagnai of UIC's department of biochemistry and molecular genetics and Abul B.M.M.K. Islam of the University Pampeu Fabra contributed to the study. Funding was provided by grants from the National Institutes of Health and the Spanish Ministerio de Educacion y Ciencia and Agència de Gestió d'Ajuts Universitaris i de Recerca of the Catalonian government and from a scholar award from the Leukemia and Lymphoma Society and a NIH National Research Service Award.
For more information about UIC, visit www.uic.edu
NOTE: Please refer to the institution as the University of Illinois at Chicago on first reference and UIC on second reference. "University of Illinois" and "U. of I." are often assumed to refer to our sister campus in Urbana-Champaign.
Jeanne Galatzer-Levy | Newswise Science News
Nanobot pumps destroy nerve agents
21.08.2018 | American Chemical Society
How do muscles know what time it is?
21.08.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.
The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
21.08.2018 | Medical Engineering
21.08.2018 | Physics and Astronomy
21.08.2018 | Power and Electrical Engineering