DRR drives brain cancer invasion by regulating cytoskeletal-focal adhesion dynamics.
Malignant glioma invasion is a primary cause of brain cancer treatment failure, yet the molecular mechanisms underlying its regulation remain elusive. We developed a novel functional-screening strategy and identified downregulated in renal cell carcinoma (DRR) as a regulator of invasion. We show that DRR drives invasion in vitro and in vivo. We found that while DRR is not expressed in normal glial cells, it is highly expressed in the invasive component of gliomas. Exploring underlying mechanisms, we show that DRR associates with and organizes the actin and microtubular cytoskeletons and that these associations are essential for focal adhesion (FA) disassembly and cell invasion. These findings identify DRR as a new cytoskeletal crosslinker that regulates FA dynamics and cell movement.
Le
P U
PU
Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Angers-Loustau
A
A
de Oliveira
R M W
RM
Ajlan
A
A
Brassard
C L
CL
Dudley
A
A
Brent
H
H
Siu
V
V
Trinh
G
G
Mölenkamp
G
G
Wang
J
J
Seyed Sadr
M
M
Bedell
B
B
Del Maestro
R F
RF
Petrecca
K
K
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D051381:Rats
C403503:FAM107A protein, human; D009687:Nuclear Proteins