Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer.
Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer.
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DOI：
10.1038/s41388-022-02420-9
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发表时间：
2022-09
期刊：
影响因子：
8
通讯作者：
Lammerding J
中科院分区：
文献类型：
--
作者：
Bell ES;Shah P;Zuela-Sopilniak N;Kim D;Varlet AA;Morival JLP;McGregor AL;Isermann P;Davidson PM;Elacqua JJ;Lakins JN;Vahdat L;Weaver VM;Smolka MB;Span PN;Lammerding J
细胞核大小和形状的异常通常被用来识别癌症组织。然而，目前尚不清楚这种紊乱的核结构是直接导致癌症病理，还是仅仅是肿瘤发生过程中发生的其他事件的结果。在这里，我们表明，高侵袭性和增殖性乳腺癌细胞经常表现出Akt驱动的核膜蛋白lamin A/C的低表达，导致核变形性增加，从而允许细胞在模拟转移过程中遇到的间质空间的受限环境中增强迁移。重要的是，高侵袭性乳腺癌细胞中层粘连蛋白A/C的表达增加反映了LMNA高表达的人乳腺肿瘤特有的基因表达变化，并特异性地影响了与细胞-ECM相互作用、细胞代谢和PI3K/Akt信号转导相关的通路。进一步支持了层粘连蛋白在乳腺癌转移中的重要作用，对人类乳腺肿瘤中层粘连蛋白水平的分析显示，层粘连蛋白A水平降低、Akt信号转导与无病生存率下降之间存在显著关联。这些发现表明，乳腺癌细胞中层蛋白A/C的下调可能会影响细胞的物理性质和促进转移的生化信号。
Aberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells frequently exhibit Akt-driven lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells reflected gene expression changes characteristic of human breast tumors with higher LMNA expression, and specifically affected pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels, Akt signaling, and decreased disease-free survival. These findings suggest that downregulation of lamin A/C in breast cancer cells may influence both cellular physical properties and biochemical signaling to promote metastatic progression.
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影响因子：
2.8
作者：
Davidson, Patricia M.;Denais, Celine;Bakshi, Maya C.;Lammerding, Jan
通讯作者：
Lammerding, Jan
DOI：
10.1007/978-1-4899-8032-8_5
发表时间：
2014-01-01
期刊：
CANCER BIOLOGY AND THE NUCLEAR ENVELOPE: RECENT ADVANCES MAY ELUCIDATE PAST PARADOXES
影响因子：
--
作者：
Bussolati, Gianni;Maletta, Francesca;Marchio, Caterina
通讯作者：
Marchio, Caterina
影响因子：
8.4
作者：
Belt, E. J. Th.;Fijneman, R. J. A.;Meijer, G. A.
通讯作者：
Meijer, G. A.
DOI：
10.1039/c5ib00200a
发表时间：
2015-12
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Davidson PM;Sliz J;Isermann P;Denais C;Lammerding J
通讯作者：
Lammerding J
影响因子：
39.3
作者：
Ali R;Wendt MK
通讯作者：
Wendt MK