LMU researchers have discovered how the interplay between a key protein and an endolysosomal ion channel promotes tumor development in skin cancer.
Ludwig-Maximilians-Universitaet Muenchen Nov 22 2024
Melanoma arising from pigment-producing cells known as melanocytes is the deadliest form of skin cancer. A major cause of melanoma is excessive exposure to ultraviolet light, from sunlight or other sources, which can trigger mutations that promote tumor formation. A team led by LMU pharmacologist Professor Christian Grimm and Dr. Karin Bartel has now investigated the molecular mechanisms of tumorigenesis.
Studies have shown that certain activity-boosting mutations in the ion channel TPC2 are associated with fair skin, blond hair, and albinism. These traits make people particularly susceptible to melanoma, as their skin offers less protection against harmful ultraviolet radiation. Conversely, loss of TPC2 is associated with decreased melanoma risk.
Molecular pathways influencing tumor progression Like TPC2, the protein Rab7a is an important regulator for the endolysosomal system. Earlier proteome analyses had shown, moreover, that Rab7a is a potential interaction partner of TPC2.
Our results show that Rab7a, by amplifying TPC2 activity, plays a key role in the regulation of tumor growth. Specifically, the activation of TPC2 by Rab7a reduces the levels of a certain protein. This protein boosts the stability of a transcription factor that is a key regulator in melanocytes and melanomas and promotes their proliferation and survival.
Skin Skin Cancer Ion Ion Channel Melanoma Melanoma Cells Metastasis Protein Tumor
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