Differential PAX3 functions in normal skin melanocytes and melanoma cells
Differential PAX3 functions in normal skin melanocytes and melanoma cells
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DOI：
10.1016/j.bbrc.2011.07.053
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发表时间：
2011-08-12
影响因子：
3.1
通讯作者：
Ziman, Mel
中科院分区：
文献类型：
--
作者：
Medic, Sandra;Rizos, Helen;Ziman, Mel
PAX3转录因子是胚胎发生过程中黑素细胞发育的关键调节因子，也经常在黑色素瘤细胞中发现。虽然已知PAX3在发育过程中调节黑素细胞的分化、存活、增殖和迁移，但尚不清楚其功能是否在成人黑素细胞和黑色素瘤细胞中得以维持。为了澄清这一点，我们评估了PAX3在这些细胞中靶向哪些基因。我们在这里表明，与其在发育中的作用类似，PAX3调节黑色素瘤细胞和黑色素细胞的复杂分化网络，以维持细胞的“干细胞”样（通过NES和SOX9）。我们还表明，迁移介质（MCAM和CSPG4）在两种细胞类型中都是常见的，但在黑色素瘤细胞中更为常见。相比之下，pax3介导的黑色素瘤细胞增殖（通过TPD52）和存活（通过BCL2L1和PTEN）的调节与黑色素细胞不同。这些结果表明，通过控制细胞增殖、存活和迁移以及维持分化程度较低的“干细胞”样表型，PAX3可能有助于黑色素瘤的发生和进展。(C) 2011爱思唯尔公司版权所有。
The PAX3 transcription factor is the key regulator of melanocyte development during embryogenesis and is also frequently found in melanoma cells. While PAX3 is known to regulate melanocyte differentiation, survival, proliferation and migration during development, it is not clear if its function is maintained in adult melanocytes and melanoma cells. To clarify this we have assessed which genes are targeted by PAX3 in these cells. We show here that similar to its roles in development, PAX3 regulates complex differentiation networks in both melanoma cells and melanocytes, in order to maintain cells as "stem" cell-like (via NES and SOX9). We show also that mediators of migration (MCAM and CSPG4) are common to both cell types but more so in melanoma cells. By contrast, PAX3-mediated regulation of melanoma cell proliferation (through TPD52) and survival (via BCL2L1 and PTEN) differs from that in melanocytes. These results suggest that by controlling cell proliferation, survival and migration as well as maintaining a less differentiated "stem" cell like phenotype, PAX3 may contribute to melanoma development and progression. (C) 2011 Elsevier Inc. All rights reserved.