Erdr1 Suppresses Murine Melanoma Growth via Regulation of Apoptosis

Abstract

Melanoma, one of the aggressive cancers, is known to be resistant to chemotherapy. Because of its aggressive nature, effectively inducing apoptosis is necessary to treat melanoma. Erythroid differentiation regulator 1 (Erdr1) is known to be a stress-related survival factor exhibiting anti-cancer effects in several cancers. However, little is known about the functions and underlying mechanisms of Erdr1 so far. To demonstrate the effect of Erdr1 in melanoma apoptosis, recombinant murine Erdr1 was injected into mice implanted with B16F10 melanoma cells. In vivo tumor growth was significantly inhibited in mice injected with Erdr1 compared to the control. In addition, the tumor from Erdr1-injected mice showed an increased level of apoptosis. Accordingly, apoptosis-regulating factors including anti-apoptotic marker Bcl-2 and pro-apoptotic marker Bax in the tumor tissues were examined. As expected, the decreased level of Bcl-2 and increased level of Bax were detected in tumors within the mice injected with Erdr1. Based on the in vivo study, the role of Erdr1 in tumor apoptosis was further tested by incubating it with cells of the murine melanoma cell line B16F10. Erdr1-induced apoptosis in B16F10 cells was observed. Additionally, Erdr1 downregulated STAT3 activity, inhibiting apoptosis via regulation of the Bcl-2 family. Overall, data demonstrate that Erdr1 induced murine melanoma apoptosis through the regulation of Bcl-2 and Bax. These findings suggest that Erdr1 is a novel regulator of apoptosis in melanoma.

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“…A high concentration of Erdr1 has an inhibitory effect on growth of the BL-70 Burkitt lymphoma cell line, suggesting that Erdr1 regulates the homeostasis of cell growth [7]. Recently, the pro-apoptotic property of Erdr1 was confirmed by the demonstration that rErdr1 induces apoptosis of melanoma cells via modulation of apoptosisregulating factors, such as Bcl-2 and Bax [8]. In addition, recent studies suggest the anti-inflammatory property of Erdr1 in contrast to the pro-inflammatory effects of IL-18.…”

Therapeutic effect of erythroid differentiation regulator 1 (Erdr1) on collagen-induced arthritis in DBA/1J mouse

“…Here, we determined the anti-migratory activity of Erdr1 in synovial fibroblasts. In addition, our previous study suggests a pro-apoptotic role of Erdr1 in mouse melanoma [8], implying that Erdr1 might act as a pro-apoptotic factor in synovial fibroblasts to inhibit hyperproliferation.…”

“…A high concentration of Erdr1 has an inhibitory effect on growth of the BL-70 Burkitt lymphoma cell line, suggesting that Erdr1 regulates the homeostasis of cell growth [7]. Recently, the pro-apoptotic property of Erdr1 was confirmed by the demonstration that rErdr1 induces apoptosis of melanoma cells via modulation of apoptosis-regulating factors, such as Bcl-2 and Bax [8]. In addition, recent studies suggest the anti-inflammatory property of Erdr1 in contrast to the pro-inflammatory effects of IL-18.…”

The Role of Erythroid Differentiation Regulator 1 (ERDR1) in the Control of Proliferation and Photodynamic Therapy (PDT) Response

“…It has been reported that melanoma is extremely resistant to chemotherapy because of the low apoptotic rate in the cancer cells [21]. Recently, the ERDR1 protein was found to enhance apoptosis in melanoma cells by regulating Bcl-2 and Bax expression, providing evidence for its critical role in the suppression of melanoma progression [22]. Lee et al confirmed that treatment with recombinant ERDR1 induces apoptosis via the downregulation of Bcl-2 and the upregulation of Bax in B16F10 cells in vitro [22].…”