City researchers find the pathway to cancer

BANGALORE: Researchers have achieved a breakthrough, identifying a protein pathway that triggers cancer in the human body owing to its erratic behaviour.

Researchers at Bangalore’s National Centre for Biological Sciences (NCBS) led by Satyajit Mayor and Neha Vyas have identified what is known as the Hedgehog pathway and the ways in which it forms and leads to cancer. The researchers, who have published their work in the journal, Cell, say this pathway is formed when the proteins (called hedgehog), which are separate, get drawn to each other by electrostatic interactions between amino acids present around the proteins.

A small cluster of proteins then gets formed and goes on to form a mega-cluster. This travels to other cells and creates effects that are good or bad — the cluster could be normal and help organ regeneration or tissue repair, or the cluster could get hyperactive and affect other cells, which is the sign that cancer is coming.

Simply put, the NCBS research indicates that hyperactivity of the hedgehog proteins within the human body can cause cancer and that its cluster formation has to be prevented to eliminate the possibility of hyperactivity entirely.

“Identifying the initial step that initiates the electrostatic attraction between amino acids that bring together hedgehog proteins in a cluster might help other scientists to design an anti-cancer drug that could stall a mutant hedgehog pathway in effective ways,” Neha told TOI. Such a drug could target the very source of these attractions — the amino acids that cause them — which are the first cause of cancer.

Not sure if this is the exact one, but a search on Cell yielded this:

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Article

Nanoscale Organization of Hedgehog Is Essential for Long-Range Signaling

Neha Vyas¹^,²,Debanjan Goswami¹,A. Manonmani¹^,⁴,Pranav Sharma¹^,⁵,H.A. Ranganath²^,⁶,K. VijayRaghavan¹,L.S. Shashidhara³,R. Sowdhamini¹andSatyajit Mayor¹^,^,

¹ National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bangalore 560 065, India
² Department of Studies in Zoology, University of Mysore, Mysore 570 006, India
³ Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India

Corresponding author

⁴ Present address: Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr 108, 01307 Dresden, Germany

⁵ Present address: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

⁶ Present address: Vice Chancellor's Office, Bangalore University, Bangalore 560 001, India

Summary

Hedgehog (Hh) plays crucial roles in tissue-patterning and activates signaling in Patched (Ptc)-expressing cells. Paracrine signaling requires release and transport over many cell diameters away by a process that requires interaction with heparan sulfate proteoglycans (HSPGs). Here, we examine the organization of functional, fluorescently tagged variants in living cells by using optical imaging, FRET microscopy, and mutational studies guided by bioinformatics prediction. We find that cell-surface Hh forms suboptical oligomers, further concentrated in visible clusters colocalized with HSPGs. Mutation of a conserved Lys in a predicted Hh-protomer interaction interface results in an autocrine signaling-competent Hh isoformincapable of forming dense nanoscale oligomers, interacting with HSPGs, or paracrine signaling. Thus, Hh exhibits a hierarchical organization from the nanoscale to visible clusters with distinct functions.

http://www.cell.com/abstract/S0092-8674(08)00685-5

Simply put, the NCBS research indicates that hyperactivity of the hedgehog proteins within the human body can cause cancer and that its cluster formation has to be prevented to eliminate the possibility of hyperactivity entirely.

So they find a cluster of proteins that can do good or bad what is their immediate assumption? We must find away to stop the formation of this cluster.

They already know that this cluster has a function in tissue repair but what other cellular functions might it be involved in?

What would be the detrimental effects of elimination of the formation of this cluster of proteins? Perhaps they should figure on this a bit longer.

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