- Melanomas are skin cancers that are particularly aggressive.
- The high mutation rate prevents further study on mechanisms that are involved.
- CPEB4 protein levels are very high in melanomas and it plays a selective and essential role.
The protein, CPEB4 is crucial for melanoma cell survival.
A new study in this area, published in Nature Communications, describes the roles of this protein.
The main goals of the Melanoma Group at the Spanish National Cancer Research Centre (CNIO) are to identify biomarkers of tumor progression and to validate novel therapeutic targets in melanoma.
Melanomas are skin cancers that are particularly aggressive and finding mechanisms that drive this behavior has been complicated due to the unexpectedly high mutation rate associated with this malignancy.
The group headed by Marisol Soengas, senior author of this paper, is an expert in researching the "identity" of melanomas.
"In previous studies, we have demonstrated that melanomas are very different from other types of tumors in that they activate mechanisms of self-degradation (autophagy), or control the internalization and secretion of molecules, for example," explains Soengas.
They have now found that the CPEB4 protein, which is of great interest in the cancer field, plays a selective and essential role in melanoma cells.
In broad terms, CPEBs are involved in the regulation of gene expression and are associated with important cellular processes, such as cell division, cell differentiation, or cell polarity and migration.
In tumors, the expression of CPEBs varies, and seemingly opposing, pro- and anti-tumour, roles have been described in other tumor types but not in melanoma.
CPEB4, a member of this family, was "especially attractive" to the authors "given its overexpression in tumors such as gliomas and pancreatic carcinomas, which are also aggressive.
As they noted, the levels of this protein were very high in melanoma from the early stages of the disease, which made the researchers suspect its association with cell proliferation.
Soengas' group compared the effects of CEPB4 on various tumors, and noted that melanoma cells were "more dependent on this protein", since its inhibition greatly hindered the proliferation of these cells.
This 'addiction' makes melanoma more vulnerable to drugs targeting this pathway, and can be a novel target for therapeutic intervention in melanoma.
The researchers also describe that melanomas depend so tightly on CPEB4 because this protein regulates the expression of factors such as MITF and RAB27A, which have unique functions in this tumour type. CPEB4, is therefore a main driver of the "intrinsic signature" that separates melanomas from other pathologies.