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Team uses antisense technology that exploits gene splicing mechanism to kill cancer cells
Date:10/31/2012

Cold Spring Harbor, N.Y. Cancer cells grow fast. That's an essential characteristic of what makes them cancer cells. They've crashed through all the cell-cycle checkpoints and are continuously growing and dividing, far outstripping our normal cells. To do this they need to speed up their metabolism.

CSHL Professor Adrian Krainer and his team have found a way to target the cancer cell metabolic process and in the process specifically kill cancer cells.

Nearly 90 years ago the German chemist and Nobel laureate Otto Warburg proposed that cancer's prime cause was a change in cell metabolism i.e., in cells' production and consumption of energy. In particular cancer cells have a stubborn propensity to eschew using glucose as a source to generate energy. This is known as the Warburg Effect.

While metabolic changes are an important feature in the transformation of normal cells into cancer cells they are not now thought to be cancer's primary cause. Despite this, metabolic changes remain an attractive target for cancer therapy, as Krainer and colleagues show in a paper published online today in Open Biology, the open-access journal of Great Britain's Royal Society.

One difference between metabolism in cancer and normal cells is the switch in cancer to the production of a different version, or isoform, of a protein produced from the pyruvate kinase-M (PK-M) gene. The protein version produced in normal cells is known as PK-M1, while the one produced by cancer cells is known as PK-M2.

PK-M2 is highly expressed in a broad range of cancer cells. It enables the cancer cell to consume far more glucose than normal, while using little of it for energy. Instead, the rest is used to make more material with which to build more cancer cells.

PK-M1 and PK-M2 are produced in a mutually exclusive manner -- one-at-a-time, from the same gene, by a mechanism known as alternative splicing. When a gene's DNA is being copied i
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Contact: Edward Brydon Ph.D.
ebrydon@cshl.edu
917-476-6633
Cold Spring Harbor Laboratory
Source:Eurekalert

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