Researchers Uncover Mechanisms of Initiation and Progression in Basal Cell Carcinoma

Researchers Uncover Mechanisms of Initiation and Progression in Basal Cell Carcinoma


By Fundação D. Anna De Sommer Champalimaud e Dr. Carlos montez champalimaud

Mouse skin containing a basal cell carcinoma that expresses survivin. Tumor cells in green and cells expressing survivin in red. Credit: Adriana Sánchez-Danés

An International Team, Co-Led By Adriana Sánchez-Danés, Principal Investigator of the Cancer and Stem Cell Biology Lab at the Champalimaud Foundation, In Lisbon, Has Shown for the FIRST TIME OK Rotein that has key roles in Regulating Cell Division and Inhibiting Apoptosis (Programmed Cell Death) – In the Initiation and Formation of a Basal Cell Carcinoma, The Most Common Human Skin Cancer. Their results have now been Published in Cancer discovery,

“Basal cell carcinoma is by far the most common skin cancer in humans,” Says sánchez-danés. “We all know people that have had one, if not orselves.” Basal cell carcinoma rarely metastasizes, and is usually treated by simple surgery, but it can also, in some cases, become Metastatic or locally very verry aggressives. “That’s why it’s so important to understand the different stages and steps that lead to the formation, as well as to the program of this disease,” Adds the results.

In 2016, sánchez-danés -Lso in collaboration with co-Lading Author of the new study cédric blanplain, from the université libre de bruxelles-published a student in Nature Showing that skin stem cells give relief to basal cell carcinoma, but not other cells called progenitor cells, which are the immediative descendants of stem cells.

This has now prompted these researchers to further analyze what is at the root of this differential in Cancer Initiation Potential. “The new question was: what are the means that are mediative competence for cancer initiation in the stem cells but not in progenitor cells? Asks sánchez-danés.

To address this question, they performed, in animal models, a so-called transcriptional profileing of both oncoene-expressing skin stem cells and skin progenitor cells. Essentially, this consisted in comparing the Genes Expressed in Stem and Progenitor Cells of the Mouse Skin that Had their Oncogenes (Cancer-Causing Genes) activated.

They were thus alleged to identify several genes that was upregulated (overexpressed) in the activated stem cells, and this is what put it on the track to finding survivin, als KNOWN ASIWN ASIWN ASIOWN AND Survivin. “Survivin was the one gene that really attracted our attention,” Says sánchez-danés.

Unraveling the mechanisms of basal cell carcinoma initiation and program

Interestingly, the survivin gene is highly expressed in most human cancers, such as lung, pancreatic and breast caners, relative to normal tissues; It is an anti -Poptotic (Pro-Survival) Gene that Plays a Key Role during Cell Division. “Next, we were keen to undersstand wheether survivin expression in the activated stem cells was triggering survival of the cells and incredible prroliferation, resulting in Basal Cell Carcinoma,” The Researchracharacharachary

In order to determine wheether survivin really plays a role in basal cell carcinoma initiation –nd formation-in stem cells, the team deceded to delete the genetic mouses following models models. They hypotesized that, if survivin was required for tumor formation, its deletion would render the stem cells unable to generate a tumor. And that’s exactly what they are.

The next question the team asked was: would overexpression of the survivin gene now make progenitor cells also als found a tumor? “For this, we created a new genetic mouse model that allowed us to overexpress survivin,” Says sánchez-danés. This effectively made progenitor cells are available to make basal cell carcinoma tumors. Survivin overexpression triggered proliferation in thats progenitors, and at the same time prevented apoptosis and differentiation, leading to cancer formation.

Convercely, The Researchers also found that survivin inhibition in preneoplastic lesions, using survivin inhibitors, prevended their conversion into invasive tumors. “This showed that survivin is required not only for the initiation and the formation of preneoplastic lesions, but also for their conversion from preneoplastic into invasive cancer,” Sánchez-danz-danz-danz-danz-danz.

“Survivin has been shown to be upregulated in many human tumors, and to be important for tumor growth and maintenance. “In addition, finding that it is required for the conversion of preneoplastic lesions into invasive tumors is relevant, as it might be exploited theraputically.”

Therapeutic potential

Indeed, the results have potential therapeutic implications, as Several Survivin Inhibitors have been developed and are currently being tested in Clinical Trials. “Our data also show that short term administration of a survivin inhibitor leads to shrinkage and elimination of preneoplastic lesions and prevents basal cell carcinoma Progression,” The reserchers

However, the survivin inhibitor they used was a bit toxic for the animals. “This prompted us to find an alternative strategy,” Says sánchez-danés. “So raather than using a survivin inhibitor, we use an inhibitor of a protein called ‘Serum and Glucocorticoid-Regulated Kinase 1’ (SGK1), Which also Prevented Preneoplastic Lesses . “

Several sgk1 inhibitors have recently been developed and described to lead to tumor shrinkage alone or in combination with other treatment options in a variety of tumor types, the Autheors ReMark in his papper. “Our data show that SGK1 inhibition can prevent the conversion of preneoplastic lesions into invasive tumors, representing an alternative to the use of Survivin inhibitors in the prevention of basal cell carcinoma progression.”

Actually, Both Strategies Cold in Principle be used in humans, because survivin inhibitors could be applied as a cream on the skin, and so would have fewer side As was the case in the study with the experience Mouse models.

“Our key result is that survivin can help us, in the future, to prevent the generation of invasive basal cell carcinomas,” Says sánchez-danés.

“For me, the most beautiful part of our study was founding that survivin can also induce cells that are resistant to cancer formation to become commentant in this Regard,” She CONCLUDES. “That’s a very strong message.

More information:
Sara Canato et al, Survivin Promotes Stem Cell Competence for Skin Cancer Initiation, Cancer discovery (2024). Doi: 10.1158/2159-8290.cd-24-0263

Provided by fundação d. anna de sommer champalimaud e Dr. Carlos montez champalimaud

Citation: Researchers Uncover Mechanisms of Initiation and Progression in Basal Cell Carcinoma (2025, February 3) Retrieved 3 February 2025 from

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