期刊
JOURNAL OF CELL BIOLOGY
卷 217, 期 1, 页码 195-209出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201704102
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资金
- Human Frontier Science Program Young Investigator grant
- Cancer Research UK
- Medical Research Council [MR/M010414/1]
- MRC [MR/M010414/1] Funding Source: UKRI
- Engineering and Physical Sciences Research Council [1091572] Funding Source: researchfish
- The Francis Crick Institute [10482, 10144] Funding Source: researchfish
Centrosome amplification is a common feature of human tumors. To survive, cancer cells cluster extra centrosomes during mitosis, avoiding the detrimental effects of multipolar divisions. However, it is unclear whether clustering requires adaptation or is inherent to all cells. Here, we show that cells have varied abilities to cluster extra centrosomes. Epithelial cells are innately inefficient at clustering even in the presence of HSET/KIFC1, which is essential but not sufficient to promote clustering. The presence of E-cadherin decreases cortical contractility during mitosis through a signaling cascade leading to multipolar divisions, and its knockout promotes clustering and survival of cells with multiple centrosomes. Cortical contractility restricts centrosome movement at a minimal distance required for HSET/KIFC1 to exert its function, highlighting a biphasic model for centrosome clustering. In breast cancer cell lines, increased levels of centrosome amplification are accompanied by efficient clustering and loss of E-cadherin, indicating that this is an important adaptation mechanism to centrosome amplification in cancer.
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