期刊
JOURNAL OF CELL SCIENCE
卷 135, 期 8, 页码 -出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.259493
关键词
Cancer; Metastasis; Cell migration; Cytoskeleton; Nucleus; Nuclear envelope; Emerin; Src; Mechanotransduction
类别
资金
- Albany Medical College
- Melanoma Research Alliance (MRA) [688232]
- American Cancer Society (ACS) [RSG-20-019-01-CCG]
It has been found that increasing nuclear stiffness through elevating lamin A levels inhibits fast amoeboid migration in melanoma cells. The inner nuclear membrane protein emerin plays a key role in regulating this migration process, and its activity needs to be precisely calibrated. Interestingly, low activity of Src has been observed in cells within a confined environment, which is related to fast amoeboid migration.
When metastasizing, tumor cells must traverse environments with diverse physicochemical properties. Recently, the cell nucleus has emerged as a major regulator of the transition from mesenchymal to fast amoeboid (leader bleb-based) migration. Here, we demonstrate that increasing nuclear stiffness through elevating lamin A, inhibits fast amoeboid migration in melanoma cells. Importantly, nuclei may respond to force through stiffening. A key factor in this process is the inner nuclear membrane (INM) protein emerin. Accordingly, we determined the role of emerin in regulating fast amoeboid migration. Strikingly, we found that both the up- and downregulation of emerin results in an inhibition of fast amoeboid migration. However, when key Src phosphorylation sites were removed, upregulation of emerin no longer inhibited fast amoeboid migration. Interestingly, as measured by using a Src biosensor, activity of Src was low in cells within a confined environment. Thus, the fast amoeboid migration of melanoma cells depends on the precise calibration of emerin activity.
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