Highly invasive lung cancer cells have longer 'fingers'
Filopodia stabilized by MYO10

Date:
July 27, 2020
Source:
Emory Health Sciences
Summary:
Tiny finger-like projections called filopodia drive invasive
behavior in a rare subset of lung cancer cells. Analysis of
molecular features distinguishing leader from follower cells
focuses on filopodia and the MYO10 gene.



FULL STORY ==========================================================================
Tiny finger-like projections called filopodia drive invasive behavior
in a rare subset of lung cancer cells, researchers at Winship Cancer
Institute of Emory University have found.


==========================================================================
Adam Marcus' lab has developed innovative techniques for separating
"leaders" and "followers," subpopulations of tumor cells that cooperate
during the process of metastasis. The lab's new analysis of what molecular features distinguish leader from follower lung cancer cells focuses on filopodia. The results are published in Science Advances.

The findings could help researchers develop treatments that prevent cancer
from spreading, by understanding the rare cells within a tumor necessary
for deadly metastasis. The durable epigenetic changes that distinguish
leader cells and invasive behavior may appear in several types of cancer,
says Marcus. He is professor of hematology and medical oncology at Emory,
and associate director for basic research and shared resources at Winship.

Marcus' previous research has shown how leader cells and their more
common counterparts, follower cells, work together to create an invasive
pack. The two types of tumor cells depend upon each other for mobility
and survival, but have distinct patterns of gene activity and even
different shapes.

In particular, leader cells display longer filopodia than follower
cells. This is part of what the investigation by graduate student Emily Summerbell (who recently obtained her PhD), associate research scientist
Janna Mouw, PhD and their colleagues revealed.

"Filopodia are like the fingers of the cell, and help the cell pull its
way forward," Summerbell says.



========================================================================== Having longer filopodia is linked with a gene called MYO10, which
encodes a component of the internal cellular skeleton stabilizing
filopodia, Summerbell and Mouw found. MYO10 was the gene that was the
most up-regulated and hypomethylated in leader cells, compared with
follower cells, and both long filopodia and invasive behavior depend on
MYO10 activity.

"It was known that MYO10 was linked to invasion and metastasis, but this
is the first evidence that it is playing this specific role in a rare
subset of cells," Marcus says. "This could help us look for these rare
cells in patient tumors to gauge how potentially invasive they are."
Leader cells also secrete fibronectin, a sticky extracellular protein,
while follower cells do not. The MYO10 protein helps filopodia rearrange fibronectin molecules into fibrils, but it does not appear to interact
with fibronectin directly.

"As the leader cell filopodia pull on the extracellular matrix, they
change this matrix from a random mesh into long parallel tracks in front
of the cell, paving a road for a group of cells," Summerbell says.

Filopodia are sometimes described as resembling antennae -- or precursors
of more stable cellular structures.

"We're observing that in leader cells, filopodia are not only sensors
of the extracellular environment but also actively participate in
reorganizing the extracellular matrix," Marcus says.

Summerbell and Mouw also studied other changes that distinguish leader
cells, such as elevated expression of the Jagged1 gene. Jagged1 encodes a receptor for the Notch pathway, whose activity lies behind activation of
MYO10. MYO10 and Jagged/Notch activation may be generalizable to patient samples and other types of cancer.


========================================================================== Story Source: Materials provided by Emory_Health_Sciences. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Emily R. Summerbell, Janna K. Mouw, Joshua S. K. Bell, Christina M.

Knippler, Brian Pedro, Jamie L. Arnst, Tala O. Khatib,
Rachel Commander, Benjamin G. Barwick, Jessica Konen, Bhakti
Dwivedi, Sandra Seby, Jeanne Kowalski, Paula M. Vertino, Adam
I. Marcus. Epigenetically heterogeneous tumor cells direct
collective invasion through filopodia-driven fibronectin
micropatterning. Science Advances, 2020; 6 (30): eaaz6197 DOI:
10.1126/sciadv.aaz6197 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200727194700.htm

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