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Some brain tumors may be mediated by tiny filament on cells
Date:8/23/2009

in a subset of human tumors, but absent in others. The presence and absence correlated with the cell-signaling pathways that were activated in the tumors. This suggests, the researchers say, that, as in mice, some tumors in humans need to remove the primary cilia to grow, while other require its presence to grow.

The explanation, says the lead investigator of the medulloblastoma study, Young-Goo Han, PhD, a postdoctoral fellow in the Alvarez-Buylla lab, has to do, in part, with the way in which the primary cilium is structured and functions.

Unlike their beating cousins, known as motile cilia, or flagella -- which swish protozoa through pond water and undulate in the airways -- primary cilia are generally immobile, and function as cellular antennae. They receive signals from other cells, allowing for their transmission, in a process known as signal transduction, down a pathway of signaling proteins -- some of which are located precisely in the cilia -- into the cytoplasm, ending at the cell's nucleus, where the signals' commands are issued.

One of the key signaling molecules in development is a secreted lipoprotein known as Hedgehog, which regulates tissue patterning, cell proliferation, and many other biological processes. Recently, scientists have discovered that Hedgehog signaling functions through the primary cilium. As Hedgehog approaches a target cell, it binds to its receptor, Patched1 (Ptch1), on the cilia, opening the gate for another protein, known as Smoothened (Smo) to enter into the cilium. There, Smo, an essential activator of the Hedgehog pathway, initiates the biochemical cascade that leads to the activation of a "downstream" protein known as Gli2, which in part communicates the Hedgehog signal to the cell's nucleus.

Aberrant Hedgehog signaling is well known to lead to human cancers, including basal cell carcinoma and medulloblastoma. However, it was not known if the cilium, itself, played a role in the development of cancer
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

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