Connexins in melanoma: Potential role of Cx46 in its aggressiveness

Melanoma is the most aggressive skin cancer, and in metastatic advanced states, it is completely refractory to chemotherapy. Therefore, it is relevant to understand the molecular bases that rule their aggressiveness. Connexins (Cxs) are proteins that under normal physiological conditions participate in intercellular communication, via the exchange of signaling molecules between the cytoplasm and extracellular milieu and the exchange of ions/second messengers between the cytoplasm of contacting cells. These proteins have shown important roles in cancer progression, chemo- and radiotherapy resistance, and metastasis. Accordingly, Cx26 and Cx43 seem to play important roles in melanoma progression and metastasis. On the other hand, Cx46 is typically expressed in the eye lens, where it seems to be associated with oxidative stress protection in fiber lens cells. However, in the last decade, Cx46 expression has been associated with breast and brain cancers, due to its role in potentiation of both extracellular vesicle release and cancer stem cell-like properties. In this review, we analyzed a potential role of Cx46 as a new biomarker and therapeutic target in melanoma.

Automated summary

Melanoma is an aggressive skin cancer that is refractory to chemotherapy in advanced stages, making it important to understand the molecular basis of its aggressiveness. Connexins (Cxs) play important roles in cancer progression and metastasis, with Cx26 and Cx43 being key players in melanoma progression, while Cx46, typically expressed in the eye lens, has been associated with cancer stem cell properties and extracellular vesicle release in breast and brain cancers in recent years. The potential role of Cx46 as a new biomarker and therapeutic target in melanoma is analyzed in this review.