Reprogramming cancer with a code

September 8, 2015

Researchers at Mayo Clinic’s Jacksonville, Fla., campus reported a discovery that could be the code for reprogramming cancer cells back to normal.

Researchers at Mayo Clinic’s Jacksonville, Fla., campus reported recently on a discovery that could be the code for reprogramming cancer cells back to normal.

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The study, published online August 24, 2015 in Nature Cell Biology, describes a new basic mechanism of epithelial cells and tissues, which could apply to all epithelial cancers, which make up 70 percent of all cancers, according to study author Antonis Kourtidis, Ph.D., a research associate in Mayo Clinic’s department of cancer biology.

“So far, … we have only tested these findings in breast and bladder cancers, with encouraging results,” Dr. Kourtidis told Dermatology Times. “We have not tested it in any types of skin cancer, yet. However, since skin is of epithelial origin, it is possible that our findings could be relevant there, as well.”

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The researchers report that adhesion proteins E-cadherin and p120 catenin (p120) - long thought to be tumor suppressors - are capable of pro-tumorigenic activities. That’s in addition to being essential in the formation of normal epithelial tissues.

“That led us to believe that these molecules have two faces - a good one, maintaining the normal behavior of the cells, and a bad one that drives tumorigenesis,” says the study’s senior investigator, Panos Anastasiadis, Ph.D., chair of the department of cancer biology at Mayo Clinic Florida.

In essence, the work pinpoints a mechanism through which adhesion complexes regulate cellular behavior, revealing their startling association with the microprocessor. The scientists resolve this “apparent paradox by identifying two spatially and functionally distinct junctional complexes in non-transformed polarized epithelial cells…,” according to the study’s abstract.

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They found the protein PLEKHA7, which associates with E-cadherin and p120 at the apical part of normal polarized epithelial cells, was regulating the behavior. PLEKHA7, they discovered, maintains cells’ normal state via a miRNA set. But loss of PLEKHA7 disrupts the adhesion complex, mis-regulates the miRNA set and switches E-cadherin and p120 from normal to oncogenic.

“We believe that loss of the apical PLEKHA7-microprocessor complex is an early and somewhat universal event in cancer,” Dr. Anastasiadis says. “In the vast majority of human tumor samples we examined, this apical structure is absent, although E-cadherin and p120 are still present. This produces the equivalent of a speeding car that has a lot of gas (the bad p120) and no brakes (the PLEKHA7-microprocessor complex).”

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Early indications in experiments on some aggressive cancer types show promise that administering the affected miRNAs in cancer cells to restore their normal levels reestablishes normal cell function, according to the authors.

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