Department of Molecular Biology, University of Wyoming, 1000 E. University Avenue, Laramie, WY, 82071, USA.
Sci Rep. 2021 Dec 8;11(1):23586. doi: 10.1038/s41598-021-02803-0.
While changes in nuclear structure and organization are frequently observed in cancer cells, relatively little is known about how nuclear architecture impacts cancer progression and pathology. To begin to address this question, we studied Nuclear Transport Factor 2 (NTF2) because its levels decrease during melanoma progression. We show that increasing NTF2 expression in WM983B metastatic melanoma cells reduces cell proliferation and motility while increasing apoptosis. We also demonstrate that increasing NTF2 expression in these cells significantly inhibits metastasis and prolongs survival of mice. NTF2 levels affect the expression and nuclear positioning of a number of genes associated with cell proliferation and migration, and increasing NTF2 expression leads to changes in nuclear size, nuclear lamin A levels, and chromatin organization. Thus, ectopic expression of NTF2 in WM983B metastatic melanoma abrogates phenotypes associated with advanced stage cancer both in vitro and in vivo, concomitantly altering nuclear and chromatin structure and generating a gene expression profile with characteristics of primary melanoma. We propose that NTF2 is a melanoma tumor suppressor and could be a novel therapeutic target to improve health outcomes of melanoma patients.
虽然在癌细胞中经常观察到核结构和组织的变化，但对于核结构如何影响癌症的进展和病理学知之甚少。为了开始解决这个问题，我们研究了核转运因子 2（NTF2），因为它的水平在黑色素瘤进展过程中会下降。我们发现，在 WM983B 转移性黑色素瘤细胞中增加 NTF2 的表达会降低细胞增殖和迁移能力，同时增加细胞凋亡。我们还证明，在这些细胞中增加 NTF2 的表达可显著抑制转移并延长小鼠的存活时间。NTF2 的水平会影响与细胞增殖和迁移相关的许多基因的表达和核定位，而增加 NTF2 的表达会导致核大小、核层 A 水平和染色质组织的变化。因此，在 WM983B 转移性黑色素瘤中异位表达 NTF2 可在体外和体内消除与晚期癌症相关的表型，同时改变核和染色质结构，并产生具有原发性黑色素瘤特征的基因表达谱。我们提出 NTF2 是一种黑色素瘤肿瘤抑制因子，可能是改善黑色素瘤患者健康状况的新的治疗靶点。
