Extracellular matrix-specific Caveolin-1 phosphorylation on tyrosine 14 is linked to augmented melanoma metastasis but not tumorigenesis

Ortiz, Rina, Diaz, Jorge, Diaz, Natalia, Lobos-Gonzalez, Lorena, Cardenas, Areli, Contreras, Pamela, Ines Diaz, Maria, Otte, Ellen, Cooper-White, Justin, Torres, Vicente, Leyton, Lisette and Quest, Andrew F. G. (2016) Extracellular matrix-specific Caveolin-1 phosphorylation on tyrosine 14 is linked to augmented melanoma metastasis but not tumorigenesis. Oncotarget, 7 26: 40571-40593. doi:10.18632/oncotarget.9738

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Author Ortiz, Rina
Diaz, Jorge
Diaz, Natalia
Lobos-Gonzalez, Lorena
Cardenas, Areli
Contreras, Pamela
Ines Diaz, Maria
Otte, Ellen
Cooper-White, Justin
Torres, Vicente
Leyton, Lisette
Quest, Andrew F. G.
Title Extracellular matrix-specific Caveolin-1 phosphorylation on tyrosine 14 is linked to augmented melanoma metastasis but not tumorigenesis
Journal name Oncotarget   Check publisher's open access policy
ISSN 1949-2553
Publication date 2016-06
Sub-type Article (original research)
DOI 10.18632/oncotarget.9738
Open Access Status File (Publisher version)
Volume 7
Issue 26
Start page 40571
End page 40593
Total pages 23
Place of publication Albany, NY United States
Publisher Impact Journals
Collection year 2017
Language eng
Abstract Caveolin-1 (CAV1) is a scaffolding protein that plays a dual role in cancer. In advanced stages of this disease, CAV1 expression in tumor cells is associated with enhanced metastatic potential, while, at earlier stages, CAV1 functions as a tumor suppressor. We recently implicated CAV1 phosphorylation on tyrosine 14 (Y14) in CAV1-enhanced cell migration. However, the contribution of this modification to the dual role of CAV1 in cancer remained unexplored. Here, we used in vitro [2D and transendothelial cell migration (TEM), invasion] and in vivo (metastasis) assays, as well as genetic and biochemical approaches to address this question in B16F10 murine melanoma cells. CAV1 promoted directional migration on fibronectin or laminin, two abundant lung extracellular matrix (ECM) components, which correlated with enhanced Y14 phosphorylation during spreading. Moreover, CAV1-driven migration, invasion, TEM and metastasis were ablated by expression of the phosphorylation null CAV1(Y14F), but not the phosphorylation mimicking CAV1(Y14E) mutation. Finally, CAV1-enhanced focal adhesion dynamics and surface expression of beta1 integrin were required for CAV1-driven TEM. Importantly, CAV1 function as a tumor suppressor in tumor formation assays was not altered by the Y14F mutation. In conclusion, our results provide critical insight to the mechanisms of CAV1 action during cancer development. Specific ECM-integrin interactions and Y14 phosphorylation are required for CAV1-enhanced melanoma cell migration, invasion and metastasis to the lung. Because Y14F mutation diminishes metastasis without inhibiting the tumor suppressor function of CAV1, Y14 phosphorylation emerges as an attractive therapeutic target to prevent metastasis without altering beneficial traits of CAV1.
Keyword Caveolin-1
Cancer
Dual role
Migration
Invasion
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Australian Institute for Bioengineering and Nanotechnology Publications
 
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