Dataset Information

The ShcA adapter protein cooperates with LPP to mediate adhesion dynamics and invadopodia formation

ABSTRACT: ShcA and Lipoma Preferred Partner (LPP) are mediators of TGFβ-induced breast cancer cell migration and invasion. Reduced expression of either protein results in diminished breast cancer lung metastasis. Total internal reflection fluorescence (TIRF) microscopy reveals that TGFβ enhances the assembly and disassembly rates of paxillincontaining adhesions in a ShcA-dependent manner through the phosphorylation of specific ShcA tyrosine residues (Y239/Y240/Y313). Using a BioID proximity labeling approach, we show that ShcA exists in a complex with a variety of actin cytoskeletal proteins, including paxillin and LPP. Consistent with a functional interaction between ShcA and LPP, TGFβ-induced LPP localization to adhesions depends on ShcA. Once localized to cellular adhesions, LPP is required to mediate TGFβ-induced cell migration and adhesion dynamics. Mutations that impair LPP localization to adhesions (mLIM1) or interaction with the actin cytoskeleton via α-actinin (ΔABD) abrogate migratory responses to TGFβ. Live-cell TIRF microscopy reveals that ShcA clustering at the cell membrane precedes LPP recruitment. We hypothesize that ShcA promotes the formation of small, dynamic adhesions in the presence of TGFβ by acting as a nucleator of focal complex formation. Finally, we define a previously unknown function for ShcA in the formation of invadopodia, a process that also requires LPP. Our data reveals that ShcA controls the formation and function of two key cellular structures required for breast cancer metastasis.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Kevin Jacquet

LAB HEAD: Claire M. Brown

PROVIDER: PXD018265 | Pride | 2020-04-27

REPOSITORIES: Pride

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			Action	DRS
	Ingel21600 (F064185).mzid_Ingel21600_(F064185).pride.mgf.gz	Mzid
	Ingel21600 (F064185).pride.mztab.gz	Mztab
	Ingel21600F064185.mzid.gz	Mzid
	Ingel21600F064185.mzid_Ingel21600_F064185.MGF	Mzid
	Ingel21600F064185.mzid_Ingel21600_F064185.RAW	Mzid

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The SHCA adapter protein cooperates with lipoma-preferred partner in the regulation of adhesion dynamics and invadopodia formation.

Kiepas Alex A Voorand Elena E Senecal Julien J Ahn Ryuhjin R Annis Matthew G MG Jacquet Kévin K Tali George G Bisson Nicolas N Ursini-Siegel Josie J Siegel Peter M PM Brown Claire M CM

The Journal of biological chemistry 20200416 31

SHC adaptor protein (SHCA) and lipoma-preferred partner (LPP) mediate transforming growth factor β (TGFβ)-induced breast cancer cell migration and invasion. Reduced expression of either protein diminishes breast cancer lung metastasis, but the reason for this effect is unclear. Here, using total internal reflection fluorescence (TIRF) microscopy, we found that TGFβ enhanced the assembly and disassembly rates of paxillin-containing adhesions in an SHCA-dependent manner through the phosphorylation ...[more]

PMID: 32299913

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