PXD013757

PXD013757 is an original dataset announced via ProteomeXchange.

Title	Proteome of Human breast cancer cell line (MDA-MB-231) with sileced MASTL vs NT control
Description	MASTL (Microtubule associated serine-threonine kinase-like) is a relatively recently identified mitotic accelerator. There are also indications of its role in cancer progression, especially in breast cancer, but the molecular mechanisms behind this and the cell cycle independent functions of MASTL are poorly understood. Regulation of cell adhesion and actin dynamics play a central role in governing cell contractility, migration and cell division in normal and cancer cells. Here, we identify MASTL as regulator of cell contractility and activator of the transcriptional co-activator MTRF-A. We show that depletion of MASTL increases cell contact with the extracellular matrix, reduces contractile actin stress fibers in normal and breast cancer cells. Importantly, depletion of MASTL also leads to strongly impairs motility of breast cancer cells. Our transcriptome and proteome profiling revealed that depletion of MASTL impairs transcription and expression of several MRTF-A target genes implicated in cellular movement and actomyosin contraction, including Rho Guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and tropomyosin 4.2 (TPM4). Mechanistically, we find that MASTL is necessary for serum-induced activation of SRF/MTRF-A transcription and that exogenous expression of GEF-H1 in MASTL depleted cells is sufficient to restore cell contractility. Taken together, our results suggest that MASTL is a previously undescribed key regulator of cell morphology and the actin cytoskeleton through transcriptional control of multiple adhesion and actin cytoskeleton regulating genes with key roles in contractility, cell adhesion and migration. MASTL (Microtubule associated serine-threonine kinase-like) is a relatively recently identified mitotic accelerator. There are also indications of its role in cancer progression, especially in breast cancer, but the molecular mechanisms behind this and the cell cycle independent functions of MASTL are poorly understood. Regulation of cell adhesion and actin dynamics play a central role in cell migration, morphology and cancer progression, but the role of MASTL in these processes has not been evaluated. Here, we show that depletion of MASTL increases cell contact with the extracellular matrix in breast cancer cells. Importantly, depletion of MASTL also leads to reduction of contractile actin stress fibers and decreased cell motility. Further, our transcriptome and proteome profiling revealed that mechanistically depletion of MASTL impairs transcription and expression of regulators of cellular movement and actomyosin contraction, including Rho Guanine nucleotide exchange factor 2 (GEF-H1, ARHGEF2) and tropomyosin 4.2 (TPM4). Further, we show that the transcriptional changes are caused by defectiveness of the serum response factor (SRF) signalling. Importantly, this study reveals advanced role for MASTL in interphase cells that activates a transcriptional program strongly impacting on the expression of regulators of cellular motility and actomyosin contraction.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:02:10.024.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfoxide; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-07 08:14:25	ID requested
1	2020-04-14 06:15:01	announced
2	2020-07-14 23:15:01	announced	2020-07-15: Updated publication reference for PubMed record(s): 32311005.
⏵ 3	2024-10-22 05:02:14	announced	2024-10-22: Updated project metadata.

10.1083/jcb.201906204;

Taskinen ME, N, ä, rv, ä E, Conway JRW, Hinojosa LS, Lilla S, Mai A, De Franceschi N, Elo LL, Grosse R, Zanivan S, Norman JC, Ivaska J, MASTL promotes cell contractility and motility through kinase-independent signaling. J Cell Biol, 219(6):(2020) [pubmed]

submitter keyword: breast cancer, cell contractility, cell migration, SILAC,MASTL, cell adhesion

Sara Rossana Zanivan
contact affiliation	CRUK - Beatson Institute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/04/PXD013757

PRIDE project URI

• PRIDE
  1. PXD013757
     1. Label: PRIDE project
     2. Name: Proteome of Human breast cancer cell line (MDA-MB-231) with sileced MASTL vs NT control