Breakthrough in Melanoma Research: Scientists Uncover Critical Protein Partnership in Cancer Development
Scientists at LMU have uncovered a crucial mechanism in skin cancer development, specifically involving the interaction between a protein and an ion channel in cell structures called endolysosomes.
Melanoma, which develops from melanocytes (pigment-producing cells), represents the most dangerous form of skin cancer. This condition typically results from excessive UV radiation exposure, whether from natural sunlight or artificial sources, leading to cancer-promoting mutations. Research conducted by Professor Christian Grimm and Dr. Karin Bartel’s team has revealed that two specific proteins – the TPC2 ion channel and the Rab7a enzyme – work together to facilitate melanoma growth and spread.
Research has identified that certain mutations enhancing TPC2 activity are linked to physical characteristics such as fair skin, blond hair, and albinism, which increase melanoma susceptibility due to reduced UV protection. The absence of TPC2, however, correlates with lower melanoma risk. This ion channel’s primary function involves regulating protein breakdown in endolysosomes, which affects tumor growth signaling pathways.
The team discovered that Rab7a, like TPC2, plays a vital role in endolysosomal regulation. Using advanced techniques including endolysosomal patch-clamp electrophysiology and fluorescence microscopy, they confirmed a functional relationship between these two proteins that enhances melanoma cell growth and invasion. They found that blocking Rab7a reduced TPC2 activity and subsequently inhibited melanoma growth.
The research revealed that Rab7a enhances TPC2 activity, which in turn affects protein levels that influence melanocyte and melanoma cell growth and survival. This finding was further validated through mouse studies, where specimens lacking either Rab7a or TPC2 showed significantly reduced tumor growth and metastasis. These discoveries suggest potential new therapeutic approaches targeting these specific cellular pathways to combat melanoma progression and spread.
