Katoh Daiki, Nishizuka Makoto, Osada Shigehiro, Imagawa Masayoshi
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan.
PLoS One. 2015 Feb 11;10(2):e0117197. doi: 10.1371/journal.pone.0117197. eCollection 2015.
Metastasis is the main cause of death in patients with cancer, and understanding the mechanisms of metastatic processes is essential for the development of cancer therapy. Although the role of several cell adhesion, migration or proliferation molecules in metastasis is established, a novel target for cancer therapy remains to be discovered. Previously, we reported that fad104 (factor for adipocyte differentiation 104), a regulatory factor of adipogenesis, regulates cell adhesion and migration. In this report, we clarify the role of fad104 in the invasion and metastasis of cancer cells. The expression level of fad104 in highly metastatic melanoma A375SM cells was lower than that in poorly metastatic melanoma A375C6 cells. Reduction of fad104 expression enhanced the migration and invasion of melanoma cells, while over-expression of FAD104 inhibited migration and invasion. In addition, melanoma cells stably expressing FAD104 showed a reduction in formation of lung colonization compared with control cells. FAD104 interacted with STAT3 and down-regulated the phosphorylation level of STAT3 in melanoma cells. These findings together demonstrate that fad104 suppressed the invasion and metastasis of melanoma cells by inhibiting activation of the STAT3 signaling pathway. These findings will aid a comprehensive description of the mechanism that controls the invasion and metastasis of cancer cells.
转移是癌症患者死亡的主要原因，了解转移过程的机制对于癌症治疗的发展至关重要。尽管几种细胞黏附、迁移或增殖分子在转移中的作用已得到证实，但仍有待发现新的癌症治疗靶点。此前，我们报道了脂肪生成调节因子fad104（脂肪细胞分化因子104）可调节细胞黏附和迁移。在本报告中，我们阐明了fad104在癌细胞侵袭和转移中的作用。高转移性黑色素瘤A375SM细胞中fad104的表达水平低于低转移性黑色素瘤A375C6细胞。fad104表达的降低增强了黑色素瘤细胞的迁移和侵袭，而FAD104的过表达则抑制了迁移和侵袭。此外，与对照细胞相比，稳定表达FAD104的黑色素瘤细胞肺定植形成减少。FAD104与STAT3相互作用并下调黑色素瘤细胞中STAT3的磷酸化水平。这些发现共同表明，fad104通过抑制STAT3信号通路的激活来抑制黑色素瘤细胞的侵袭和转移。这些发现将有助于全面描述控制癌细胞侵袭和转移的机制。
