Jordana Jampel

DocwireNews

Melanoma that proliferates from pigment-producing melanocytes is the deadliest form of skin cancer, which can be caused by extensive ultraviolet light exposure, especially in individuals with low levels of melanin. A team led by Professor Christian Grimm and Dr. Karen Bartel investigated the molecular mechanisms of tumorigenesis, revealing the interplay between two proteins, the ion channel TPC2 and the enzyme Rab7a, promote melanoma growth and metastasis. The results were <a href="https://www.nature.com/articles/s41467-024-54324-9">published</a> in Nature Communications.
Mutations in the ion channel TPC2, which increase its activity, are linked to traits like fair skin, blond hair, and albinism. These characteristics make individuals more vulnerable to melanoma, as their skin is less protective against UV radiation. Conversely, the absence of TPC2 reduces melanoma risk.
TPC2 plays a key role in breaking down proteins within endolysosomes, cell structures involved in transport and degradation, which influences the signaling pathways responsible for regulating tumor growth.
Similar to TPC2, Rab7a is a crucial regulator of the endolysosomal system. Previous proteome analyses indicated that Rab7a may interact with TPC2. The researchers confirmed this interaction using advanced techniques like endolysosomal patch-clamp electrophysiology and fluorescence microscopy. They found that Rab7a enhanced TPC2 activity, promoting melanoma cell growth and invasiveness. In contrast, inhibiting Rab7a reduced TPC2 activity, slowing melanoma progression.
“Our results show that Rab7a, by amplifying TPC2 activity, plays a key role in the regulation of tumor growth,” Grimm <a href="https://www.lmu.de/en/newsroom/news-overview/news/scientists-identify-key-mechanism-in-development-of-skin-cancer.html">noted</a>. “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.”

Melanoma that proliferates from pigment-producing melanocytes is the deadliest form of skin cancer, which can be caused by extensive ultraviolet light exposure, especially in individuals with low levels of melanin. A team led by Professor Christian Grimm and Dr. Karen Bartel investigated the molecular mechanisms of tumorigenesis, revealing the interplay between two proteins, the ion channel TPC2 and the enzyme Rab7a, promote melanoma growth and metastasis. The results were <a href="https://www.nature.com/articles/s41467-024-54324-9">published</a> in Nature Communications.Mutations in the ion channel TPC2, which increase its activity, are linked to traits like fair skin, blond hair, and albinism. These characteristics make individuals more vulnerable to melanoma, as their skin is less protective against UV radiation. Conversely, the absence of TPC2 reduces melanoma risk.TPC2 plays a key role in breaking down proteins within endolysosomes, cell structures involved in transport and degradation, which influences the signaling pathways responsible for regulating tumor growth.Similar to TPC2, Rab7a is a crucial regulator of the endolysosomal system. Previous proteome analyses indicated that Rab7a may interact with TPC2. The researchers confirmed this interaction using advanced techniques like endolysosomal patch-clamp electrophysiology and fluorescence microscopy. They found that Rab7a enhanced TPC2 activity, promoting melanoma cell growth and invasiveness. In contrast, inhibiting Rab7a reduced TPC2 activity, slowing melanoma progression.“Our results show that Rab7a, by amplifying TPC2 activity, plays a key role in the regulation of tumor growth,” Grimm <a href="https://www.lmu.de/en/newsroom/news-overview/news/scientists-identify-key-mechanism-in-development-of-skin-cancer.html">noted</a>. “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.”

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