Study: TPC2 Ion Channel Key Driver of Melanoma Progression
Key Takeaways
The PC2 ion channel regulates critical intracellular trafficking pathways and has an impact on melanoma cell survival, proliferation, and invasiveness.
Loss of TPC2 impairs Rab7-mediated endosomal transport, altering β-Catenin and MITF signaling (this can alter melanoma growth and adaptation).
Targeting TPC2 offers a potential target for melanoma treatment, with potential to complement other treatments by addressing the cancer's basic survival mechanisms.
New research has succeeded in identifying a critical regulator of melanoma progression.
The research, published by a group from Ludwig-Maximilians-Universität München in Nature Communications, highlights how TPC2 influences intracellular trafficking pathways that drive melanoma cell survival, proliferation, and invasiveness.
According to the paper, TPC2 disruption impairs late-endosome transport mediated by Rab7 (a key process in cellular signaling), which alters the activity of β-Catenin and MITF (two transcription factors essential for melanoma progression). Functional assays revealed that silencing the TPC2 pathway in melanoma cells resulted in reduced invasiveness and slower growth.
Using advanced molecular techniques to dissect TPC2's function (CRISPR-Cas9 gene editing, live-cell imaging, and more), the researchers confirmed that TPC2 regulation of endosomal pathways significantly influences how melanoma cells respond to their environment. By impairing β-Catenin and MITF activity, TPC2 disruption interferes with gene networks that support tumor growth and adaptation.
“Our results show that Rab7a, by amplifying TPC2 activity, plays a key role in the regulation of tumor growth,” said LMU pharmacologist Professor Christian Grimm, of the Walther Straub Institute of Pharmacology and Toxicology, in a press release about the study. “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.”
Source: Abrahamian C, et al. Nature Communications. 2024. Doi:10.1038/s41467-024-54324-9