To study the role of STIM1 protein in melanoma growth in vitro, the researchers used STIM1 knockdown mouse cells and injected them into mouse models and observed the growth of melanoma. Compared with controls, melanoma growth was reduced by as much as 75% in mice that were injected with STIM1 knockdown cells.
While trying to find novel players that could potentially regulate pigmentation, the researchers identified a few signalling pathways which were differently regulated with change in pigmentation level.
When chemicals were used to change the levels of pigmentation of melanocytes, the researchers found that along with changes in melanin levels, other signalling modules were also changing. Similarly, melanin level reduced when pigmentation decreased. A surprising finding was that when pigmentation was decreasing, the calcium signalling pathway was also decreasing. “We got a hint that the STIM1 protein, which is a key regulator of calcium signalling pathway, would be regulating pigmentation too,” says Jyoti Tanwar from IGIB and one of the authors of the paper published in The EMBO Journal.Zebrafish embryos
To confirm the role of STIM1 protein in pigmentation, the researchers knocked down the protein in melanocytes. This resulted in a reduction in pigmentation levels. “We further validated the role of STIM1 in regulating pigmentation in zebrafish models,” Dr. Motiani says. “The knockdown of STIM1 significantly decreased pigmentation in zebrafish embryos. Both in vitro and zebrafish studies established the critical role of STIM1 protein in pigmentation.”