p130Cas/BCAR1 scaffold protein in tissue homeostasis and pathogenesis

Leal, Maria del Pilar Camacho; Sciortino, Marianna; Tornillo, Giusy; Colombo, Shana; Defilippi, Paola; Cabodi, Sara

doi:10.1016/j.gene.2015.02.027

Cited by 37 publications

(29 citation statements)

References 61 publications

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“…Several of the genes showing increased chromatin accessibility across all samples have previously been shown to be associated with cancer. These include CTSB in OAC [ 23 ], BAIAP2L1 in ovarian cancer [ 24 ] and BCAR1 in a range of cancers [ 25 ]. We also examined whether we could see any transcription factor footprints in the regions occupied by ETV1 and as expected we could see a clear footprint at the ETS binding motif that is recognised by ETV1 ( Fig 4E ).…”

Section: Resultsmentioning

confidence: 99%

Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma

et al. 2017

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Oesophageal adenocarcinoma (OAC) is one of the ten most prevalent forms of cancer and is showing a rapid increase in incidence and yet exhibits poor survival rates. Compared to many other common cancers, the molecular changes that occur in this disease are relatively poorly understood. However, genes encoding chromatin remodeling enzymes are frequently mutated in OAC. This is consistent with the emerging concept that cancer cells exhibit reprogramming of their chromatin environment which leads to subsequent changes in their transcriptional profile. Here, we have used ATAC-seq to interrogate the chromatin changes that occur in OAC using both cell lines and patient-derived material. We demonstrate that there are substantial changes in the regulatory chromatin environment in the cancer cells and using this data we have uncovered an important role for ETS and AP1 transcription factors in driving the changes in gene expression found in OAC cells.

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Section: Resultsmentioning

confidence: 99%

Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma

et al. 2017

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“…p130Cas is a multifunctional adaptor protein required for embryonic development and is characterized by structural motifs that enable interactions with a variety of signaling molecules and the modulation of pathways controlling cell proliferation, survival, actin cytoskeleton organization and extracellular matrix degradation [ 1 ]. p130Cas/BCAR1 expression has been shown to be fundamental for cell transformation and tumor progression in several cancers but also in other diseases [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

Conditional ablation of p130Cas/BCAR1 adaptor protein impairs epidermal homeostasis by altering cell adhesion and differentiation

et al. 2018

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Backgroundp130 Crk-associated substrate (p130CAS; also known as BCAR1) is a scaffold protein that modulates many essential cellular processes such as cell adhesion, proliferation, survival, cell migration, and intracellular signaling. p130Cas has been shown to be highly expressed in a variety of human cancers of epithelial origin. However, few data are available regarding the role of p130Cas during normal epithelial development and homeostasis.MethodsTo this end, we have generated a genetically modified mouse in which p130Cas protein was specifically ablated in the epidermal tissue.ResultsBy using this murine model, we show that p130Cas loss results in increased cell proliferation and reduction of cell adhesion to extracellular matrix. In addition, epidermal deletion of p130Cas protein leads to premature expression of “late” epidermal differentiation markers, altered membrane E-cadherin/catenin proteins localization and aberrant tyrosine phosphorylation of E-cadherin/catenin complexes. Interestingly, these alterations in adhesive properties in absence of p130Cas correlate with abnormalities in progenitor cells balance resulting in the amplification of a more committed cell population.ConclusionAltogether, these results provide evidence that p130Cas is an important regulator of epidermal cell fate and homeostasis.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0289-z) contains supplementary material, which is available to authorized users.

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“…One of the pTyr peptides with the highest SILAC ratios (2.34) was derived from p130Cas (Bcar1) (Fig. 4B), a well-established SH3 domain containing signaling protein with an adaptor functionality 22, 23 . The SILAC ratio of the Bcar1/p130Cas pY391-peptide (RPGPGTLpYDVPR) is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

et al. 2018

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Identifying direct substrates targeted by protein kinases is important in understanding cellular physiology and intracellular signal transduction. Mass-spectrometry based quantitative proteomics provides a powerful tool for comprehensively characterizing the downstream substrates of protein kinases. This approach is efficiently applied to receptor kinases which can be precisely, directly, and rapidly activated by some agent, such as a growth factor. However, non-receptor tyrosine kinase Abl lacks the experimental advantage of extracellular growth factors as immediate and direct stimuli. To circumvent this limitation, we combine a chemical rescue approach with quantitative phosphoproteomics to identify targets of Abl and their phosphorylation sites with enhanced temporal resolution. Both known and novel putative substrates are identified, presenting opportunities for studying unanticipated functions of Abl under physiological and pathological conditions.

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p130Cas/BCAR1 scaffold protein in tissue homeostasis and pathogenesis

Cited by 37 publications

References 61 publications

Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma

Open chromatin profiling identifies AP1 as a transcriptional regulator in oesophageal adenocarcinoma

Conditional ablation of p130Cas/BCAR1 adaptor protein impairs epidermal homeostasis by altering cell adhesion and differentiation

Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of Conditionally Active Abl Kinase

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