Important advance in the fight against skin cancer

July 11, 2013, Hospital del Mar Medical Research Institute

Researchers from the Hospital del Mar Medical Research Institute (IMIM), lead by Lluís Espinosa, have identified a new function of the IB protein that is key in the development of squamous-cell carcinoma, a type of skin cancer. The study has been published in the prestigious journal Cancer Cell and provides a new tool for the diagnosis of the disease and, in the future, will enable the identification of novel therapeutic targets to treat this type of cancer.

"In this study we identified a new function of a protein that directly regulates the activity of the genes involved in and in the development of cancer" explains Lluís Espinosa, a researcher of the Stem Cells and Cancer group at IMIM, and the coordinator of the study, which also involved the participation of researchers from Hospital del Mar, Centre for Genomic Regulation and from national and international universities.

Until now, the only known function of the protein IB was in the cytoplasm where it inhibits the NF-B factor, a protein complex that is involved in the immune response. Now we have discovered that in the nucleus of keratinocytes, the typical , and also in the nucleus of , there is a different form of IB that results from its binding to another molecule called Sumo (leading to the Sumo-IB protein) that had been previously observed by other groups, but no function had been adscribed.

During the study, the authors analyzed a cohort of 112 patient samples with urogenital skin squamous-cell carcinoma at different stages of tumour progression. Results showed that in samples with invasive tumours or that had developed metastasis, IB disappeared from the nucleus. This indicated that during the tumour progression process, nuclear IB was lost and accumulated in the .

The finding of this new function of IB in the represents a change in the paradigm of this field and could even entail a re-interpretation of some previously published studies.

Every year, over 250,000 new cases of squamous-cell are diagnosed. This is the second most common type of skin cancer and it develops in the squamous cells that form the upper layers of the skin. Squamous-cell carcinoma can develop in any part of the body but it is most common in areas exposed to the sun. Until now, there were no good clinical or histological markers to predict metastasis in this type of tumour.

"Although it still has to be validated in a sufficient number of patients, the detection of this protein in skin lesions could serve as a diagnosis tool and to predict the prognosis of squamous-cell carcinoma" explains Agustí Toll, dermatologist at the Hospital del Mar and researcher at the IMIM, and one of the authors of this article. Besides being a possible biomarker for squamous-cell carcinoma prognosis, the identification of the mechanisms regulating the aggressive behaviour of skin tumours could have a therapeutic use. When metastasis occurs, the prognosis of patients with these tumours is generally poor and current treatments (surgery, radiotherapy and chemotherapy) are linked to severe side effects, especially among elderly patients. "This discovery could have a very significant impact on the treatment of this type of cancer when we identify drugs that revert the loss of nuclear IB that is observed in " says Espinosa.

The aim of the researchers is to discover the mechanisms regulating the loss of nuclear IB to identify therapeutic targets that could be used in the future to fight against skin cancer. The researchers also believe that the new mechanism could be relevant for other types of cancers.

Explore further: Researchers discover possible trigger for spread of head and neck cancer cells

More information: "Chromatin-bound IkBa regulates a subset of Polycombtarget genes in differentiation and cancer". María Carmen Mulero, Dolors Ferres-Marco, Abul Islam, Pol Margalef, Matteo Pecoraro, Agustí Toll, Nils Drechsel, Cristina Charneco, Shelly Davis, Nicolás Bellora, Fernando Gallardo, Erika López-Arribillaga, Elena Asensio-Juan, Verónica Rodilla, Jessica González, Mar Iglesias, Vincent Shih, M. Mar Albà, Luciano Di Croce, Alexander Hoffmann, Shigeki Miyamoto, Jordi Villà-Freixa, Nuria López-Bigas, William M. Keyes, María Domínguez, Anna Bigas and Lluís Espinosa. Cancer Cell.

Related Stories

Researchers discover possible trigger for spread of head and neck cancer cells

May 8, 2013
(Medical Xpress)—Very little has been known about the epigenetic events—developmental and environmental factors affecting genes—that occur prior to the invasive growth of head and neck squamous cell carcinomas and their ...

A new indicator for breast cancer relapse identified

June 19, 2012
Researchers at the IMIM (Institut de Recerca Hospital del Mar) have proven that the absence of the 14-3-3 protein sigma in breast cancer cells is directly associated with these cells' capacity to activate the signalling of ...

New drug targets for squamous cell carcinoma

May 19, 2011
Researchers at Fred Hutchinson Cancer Research Center have discovered a new drug target for squamous cell carcinoma – the second most common form of skin cancer. Scientists in the laboratory of Valeri Vasioukhin, Ph.D., ...

Misregulated genes common to tobacco-related cancers offer potential new prognostic tool

April 9, 2013
Believe it or not, while researchers have explored which genes are mutated in each type of tobacco-associated cancer, until now no one had thought to look across these types for common genes that might predict patient outcomes. ...

Researchers study how patterns, timing of sunlight exposure contribute to skin cancers

October 23, 2012
(Medical Xpress)—Researchers at Moffitt Cancer Center, the University of South Florida and the International Agency for Research on Cancer in France have studied the patterns and timing of sunlight exposure and how each ...

New drug targets skin cancer

May 7, 2013
A new class of drug targeting skin cancer's genetic material has been successfully tested in humans for the first time, opening the way to new treatments for a range of conditions from skin cancers to eye diseases.

Recommended for you

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

Dietary fat, changes in fat metabolism may promote prostate cancer metastasis

January 15, 2018
Prostate tumors tend to be what scientists call "indolent" - so slow-growing and self-contained that many affected men die with prostate cancer, not of it. But for the percentage of men whose prostate tumors metastasize, ...

Pancreatic tumors may require a one-two-three punch

January 15, 2018
One of the many difficult things about pancreatic cancer is that tumors are resistant to most treatments because of their unique density and cell composition. However, in a new Wilmot Cancer Institute study, scientists discovered ...


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.