TY - JOUR
T1 - Profilin1 regulates invadopodium maturation in human breast cancer cells
AU - Valenzuela-Iglesias, A.
AU - Sharma, V. P.
AU - Beaty, B. T.
AU - Ding, Z.
AU - Gutierrez-Millan, L. E.
AU - Roy, P.
AU - Condeelis, J. S.
AU - Bravo-Cordero, J. J.
N1 - Funding Information:
We would like to thank the members of the Condeelis, Cox and Hodgson labs for their helpful discussions and the Analytical Imaging Facility of the Gruss Lipper Biophotonics Center at Albert Einstein College of Medicine. This work was funded by CA150344 (J.C., J.J.B.C., B.T.B.), Susan G. Komen fellowship KG111405 (V.P.S.), 2R01 CA108607 (P.R.), MSTP training grant T32-GM007288 (B.T.B.).
Publisher Copyright:
© 2015 Elsevier GmbH.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Invadopodia are actin-driven membrane protrusions that show oscillatory assembly and disassembly causing matrix degradation to support invasion and dissemination of cancer cells in vitro and in vivo. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas and it is been shown that its depletion enhances invasiveness and motility of breast cancer cells by increasing PI(3,4)P2 levels at the leading edge. In this study, we show for the first time that depletion of profilin1 leads to an increase in the number of mature invadopodia and these assemble and disassemble more rapidly than in control cells. Previous work by Sharma et al. (2013a), has shown that the binding of the protein Tks5 with PI(3,4)P2 confers stability to the invadopodium precursor causing it to mature into a degradation-competent structure. We found that loss of profilin1 expression increases the levels of PI(3,4)P2 at the invadopodium and as a result, enhances recruitment of the interacting adaptor Tks5. The increased PI(3,4)P2-Tks5 interaction accelerates the rate of invadopodium anchorage, maturation, and turnover. Our results indicate that profilin1 acts as a molecular regulator of the levels of PI(3,4)P2 and Tks5 recruitment in invadopodia to control the invasion efficiency of invadopodia.
AB - Invadopodia are actin-driven membrane protrusions that show oscillatory assembly and disassembly causing matrix degradation to support invasion and dissemination of cancer cells in vitro and in vivo. Profilin1, an actin and phosphoinositide binding protein, is downregulated in several adenocarcinomas and it is been shown that its depletion enhances invasiveness and motility of breast cancer cells by increasing PI(3,4)P2 levels at the leading edge. In this study, we show for the first time that depletion of profilin1 leads to an increase in the number of mature invadopodia and these assemble and disassemble more rapidly than in control cells. Previous work by Sharma et al. (2013a), has shown that the binding of the protein Tks5 with PI(3,4)P2 confers stability to the invadopodium precursor causing it to mature into a degradation-competent structure. We found that loss of profilin1 expression increases the levels of PI(3,4)P2 at the invadopodium and as a result, enhances recruitment of the interacting adaptor Tks5. The increased PI(3,4)P2-Tks5 interaction accelerates the rate of invadopodium anchorage, maturation, and turnover. Our results indicate that profilin1 acts as a molecular regulator of the levels of PI(3,4)P2 and Tks5 recruitment in invadopodia to control the invasion efficiency of invadopodia.
KW - Matrix degradation
KW - PI(3,4)P
KW - Profilin1
KW - Tks5
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U2 - 10.1016/j.ejcb.2014.12.002
DO - 10.1016/j.ejcb.2014.12.002
M3 - Article
C2 - 25613364
AN - SCOPUS:84991931173
SN - 0171-9335
VL - 94
SP - 78
EP - 89
JO - European Journal of Cell Biology
JF - European Journal of Cell Biology
IS - 2
ER -
