In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-03-13)
Abstract:
When animals develop from embryos to adults, or try to heal wounds later in life, their cells have to move. Moving means that the cells must invade into their surroundings, a dense network of proteins called the extracellular matrix. The cell first attaches to the extracellular matrix; degrades it; and then moves into the newly opened space. Cells have developed specialized structures called invadosomes to enable all these steps. Invadosomes are never static, they first assemble where cells interact with extracellular matrix, they then release proteins that loosen the matrix, and finally disassemble again to allow cells to move. Invadosomes in cancer cells often become overactive, and can allow the tumor cells to spread throughout the body. A lot of different proteins are involved in controlling how and when cells move. p27 is a well-known protein usually found in a cell’s nucleus along with the cell’s DNA. Inside the nucleus, p27 suppresses tumor growth by stopping cells from dividing. However, often in cancer cells p27 moves outside of the cell’s nucleus where it contributes to cell movement via an unknown mechanism. To answer how p27 controls cell invasion, Jeannot et al. used a biochemical technique to uncover which proteins p27 binds to when it is outside of the nucleus. One of its interaction partners was called Cortactin. This protein is known to be an important building block of invadosomes, and is involved in both the assembly and disassembly of these structures. In further experiments, Jeannot studied mouse cells with or without p27 and human cancer cells that can be grown in the laboratory. The experiments revealed that p27 promotes an enzyme called PAK1 to also bind to Cortactin. PAK1 then modified Cortactin, causing whole invadosomes to disassemble, which in turn allowed cells to de-attach from the matrix and move forward. In contrast, cells lacking p27 had more stable invadosomes, attached more strongly to the matrix and were better at degrading it, but could not invade as well as cells with p27. Overall these experiments showed a new way that p27 promotes cell invasion. The next steps will include finding out exactly how the modification of Cortactin causes the invadosomes to disassemble. Furthermore, it will be important to study whether forcing p27 back into the nucleus can reduce the spread of cancer cells in the body.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.22207.001
DOI:
10.7554/eLife.22207.002
DOI:
10.7554/eLife.22207.003
DOI:
10.7554/eLife.22207.004
DOI:
10.7554/eLife.22207.005
DOI:
10.7554/eLife.22207.006
DOI:
10.7554/eLife.22207.007
DOI:
10.7554/eLife.22207.008
DOI:
10.7554/eLife.22207.009
DOI:
10.7554/eLife.22207.010
DOI:
10.7554/eLife.22207.011
DOI:
10.7554/eLife.22207.012
DOI:
10.7554/eLife.22207.013
DOI:
10.7554/eLife.22207.014
DOI:
10.7554/eLife.22207.015
DOI:
10.7554/eLife.22207.016
DOI:
10.7554/eLife.22207.017
DOI:
10.7554/eLife.22207.018
DOI:
10.7554/eLife.22207.019
DOI:
10.7554/eLife.22207.020
DOI:
10.7554/eLife.22207.021
DOI:
10.7554/eLife.22207.022
DOI:
10.7554/eLife.22207.023
DOI:
10.7554/eLife.22207.024
DOI:
10.7554/eLife.22207.025
DOI:
10.7554/eLife.22207.026
DOI:
10.7554/eLife.22207.027
DOI:
10.7554/eLife.22207.028
DOI:
10.7554/eLife.22207.029
DOI:
10.7554/eLife.22207.030
DOI:
10.7554/eLife.22207.031
DOI:
10.7554/eLife.22207.032
DOI:
10.7554/eLife.22207.033
DOI:
10.7554/eLife.22207.034
DOI:
10.7554/eLife.22207.035
DOI:
10.7554/eLife.22207.036
DOI:
10.7554/eLife.22207.037
DOI:
10.7554/eLife.22207.038
DOI:
10.7554/eLife.22207.039
DOI:
10.7554/eLife.22207.040
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3
Permalink