Cell differentiation as a novel strategy for the treatment of an aggressive type of skin cancer

July 9, 2012

Skin squamous cell carcinoma (SCC) is a subtype of very aggressive skin cancers that usually develops in sunexposed body regions, but can also affect a large number of organs such as the bladder, esophagus, lungs etc. However, little is known about the biology of these cells, which consequently makes difficult the generation of new specific therapies; actually, the standard treatments are based on surgery and subsequent radiotherapy.

Researchers at the Spanish National Cancer Research Centre (CNIO) led by Erwin Wagner, vice-director of Basic Research and director of BBVA Foundation-CNIO Cancer Cell Biology Programme, have discovered a molecular mechanism that favours the disappearance and inhibition of SCC development. The authors propose that these mechanisms could be crucial for the development of targeted therapies that could potentially overcome drug resistance.

The study, which also involves the participation of medical researchers at the Medical University of Vienna, Austria, is published today on the online edition of The .

"The guardian of the genome" p53, decreases cell division in favour of cell differentiation

Using in vitro models, mouse and human tumors, researchers have uncovered the by which the , also called "the guardian of the genome", prevents the formation of skin SCC tumors.

"We demonstrate for the first time that p53 promotes differentiation [cell functional specialization] of keratinocytes [the most predominant cell type in the epidermis], thus avoiding their division and providing a protective effect against tumors", states Juan Guinea Viniegra, "Ramón y Cajal" investigator at the CNIO and first author of the work.

The alteration of these pathways decreases cell differentiation and hence produces an increase in cell division. "We found that samples from patients with skin SCC show reduced activity of proteins that promote cell differentiation and an overactivation of inhibitory signals," says Guinea.

An additional contribution of this work is the use of compounds that induce at the expense of cancer cell division. "The next step is to test these molecules in mouse models of skin cancer and assess whether they impair cell division and tumor development", reveals the author.

Treatment of tumors based on differentiation therapies is a new avenue in the development of innovative cancer treatments. These therapies, unlike conventional ones, seek to transform cancer cells into differentiated cells, which remain in the body with few possibilities to divide and likely avoiding the appearance of .

Explore further: Stop signal discovered for skin cancer

More information: Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17. Juan Guinea-Viniegra, Rainer Zenz, Harald Scheuch, María Jiménez, Latifa Bakiri, Peter Petzelbauer, Erwin F. Wagner. The Journal of Clinical Investigation (2012). DOI: :10.1172/JCI63103

Related Stories

Stop signal discovered for skin cancer

November 15, 2011
(Medical Xpress) -- An extraordinary breakthrough in understanding what stops a common form of skin cancer from developing could make new cancer treatments and prevention available to the public in five years. 

Picking cancer stem cells out of the crowd

June 15, 2011
(Medical Xpress) -- Stem cells receive a vast amount of research attention due to their abilities to differentiate, heal, and divide in perpetuity, properties that yield promise for regenerative medicine. In cancer stem cells, ...

New role for Vascular Endothelial Growth Factor in regulating skin cancer stem cells

October 19, 2011
Skin squamous cell carcinomas are amongst the most frequent cancers in humans. Recent studies suggest that skin squamous cell carcinoma, like many other human cancers, contain particular cancer cells, known as cancer stem ...

Normal gene hinders breast cancer chemotherapy

June 11, 2012
Presence of normal p53, a tumor suppressor gene, instead of a mutated version, makes breast cancer chemotherapy with doxorubicin less effective. The preclinical study led by MD Anderson scientists was published today in the ...

Recommended for you

Study prompts new ideas on cancers' origins

December 16, 2017
Rapidly dividing, yet aberrant stem cells are a major source of cancer. But a new study suggests that mature cells also play a key role in initiating cancer—a finding that could upend the way scientists think about the ...

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.