PXD018265

PXD018265 is an original dataset announced via ProteomeXchange.

Title	The ShcA adapter protein cooperates with LPP to mediate adhesion dynamics and invadopodia formation
Description	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.
HostingRepository	PRIDE
AnnounceDate	2020-04-27
AnnouncementXML	Submission_2020-04-26_23:24:17.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD018265
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kevin Jacquet
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Phospho; Deamidated; phosphorylated residue; Oxidation; monohydroxylated residue; Carbamidomethyl; deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-30 04:03:00	ID requested
⏵ 1	2020-04-26 23:24:19	announced

Kiepas A, Voorand E, Senecal J, Ahn R, Annis MG, Jacquet K, Tali G, Bisson N, Ursini-Siegel J, Siegel PM, Brown CM, The SHCA adapter protein cooperates with lipoma-preferred partner in the regulation of adhesion dynamics and invadopodia formation. J Biol Chem, 295(31):10535-10559(2020) [pubmed]

submitter keyword: SHCA, ADAPTOR, ADHESION, INVASION

Claire M. Brown
contact affiliation	Department of Physiology, McGill University, Advanced BioImaging Facility (ABIF), McGill University
contact email	claire.brown@mcgill.ca
lab head
Kevin Jacquet
contact affiliation	CRC quebec
contact email	kevin.jacquet.labobisson@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018265
     1. Label: PRIDE project
     2. Name: The ShcA adapter protein cooperates with LPP to mediate adhesion dynamics and invadopodia formation