The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness

Salemme, Vincenzo; Angelini, Costanza; Chapelle, Jennifer; Centonze, Giorgia; Natalini, Dora; Morellato, Alessandro; Taverna, Daniela; Turco, Emilia; Ala, Ugo; Defilippi, Paola

doi:10.1007/s00018-020-03666-w

Cited by 7 publications

(7 citation statements)

References 83 publications

(143 reference statements)

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“…Paxillin, located at the interface between the plasma membrane and the actin cytoskeleton, is controlled by miR-137, miR-145, miR-218 and miR-125b [ 88 , 89 ]. p140Cap, a multisite docking protein co-distributed with cortical actin and actin stress fibers and absent in FA [ 90 ], is regulated by several miRNAs [ 91 ].…”

Section: Mirnas As Relevant Regulators Of Adhesion/migration/invasion...mentioning

confidence: 99%

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

Quirico

Orso

Cucinelli

et al. 2022

Cell. Mol. Life Sci.

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MicroRNAs (miRNAs) are small, non-coding RNAs about 22 nucleotides in length that regulate the expression of target genes post-transcriptionally, and are highly involved in cancer progression. They are able to impact a variety of cell processes such as proliferation, apoptosis and differentiation and can consequently control tumor initiation, tumor progression and metastasis formation. miRNAs can regulate, at the same time, metabolic gene expression which, in turn, influences relevant traits of malignancy such as cell adhesion, migration and invasion. Since the interaction between metabolism and adhesion or cell movement has not, to date, been well understood, in this review, we will specifically focus on miRNA alterations that can interfere with some metabolic processes leading to the modulation of cancer cell movement. In addition, we will analyze the signaling pathways connecting metabolism and adhesion/migration, alterations that often affect cancer cell dissemination and metastasis formation.

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Section: Mirnas As Relevant Regulators Of Adhesion/migration/invasion...mentioning

confidence: 99%

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

Quirico

Orso

Cucinelli

et al. 2022

Cell. Mol. Life Sci.

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“…While p130Cs is ubiquitously expressed, p140Cap expression is highly tissue-specific. Indeed, analyzing several tissues and cellular lines ( Di Stefano et al, 2004 ), it was apparent that the p140Cap protein is physiologically expressed in neural and epithelial tissues and in a significant subset of cancers including breast cancer and neuroblastoma ( Salemme et al, 2021 ). Interestingly, in both these types of cancers p140Cap has been demonstrated to act as tumor suppressor protein, impairing cancer properties and correlating with a better prognosis ( Di Stefano et al, 2007 ; Grasso et al, 2017 , 2020 ).…”

Section: Identification Of P140cap (P130cas-associated Protein) and Its Main Characteristicsmentioning

confidence: 99%

“…Several microRNAs (miRNAs) affect the expression of these adaptor proteins. The post-transcriptional control of p140Cap by miRNAs occurs in different types of cancer and involves many miRNAs, as extensively discussed elsewhere ( Salemme et al, 2021 ). The only miRNA that acts as a negative regulator of p140Cap in breast cancer is miR-150, which promotes cell migration, invasion, and expression of EMT markers in breast cancer cells.…”

Section: Transcriptional and Posttranscriptional Control Of P130 Crk-associated Substrate And P140cap Expressionmentioning

confidence: 99%

p130Cas/BCAR1 and p140Cap/SRCIN1 Adaptors: The Yin Yang in Breast Cancer?

Centonze

Natalini

Salemme

et al. 2021

Front. Cell Dev. Biol.

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p130Cas/BCAR1 is an adaptor protein devoid of any enzymatic or transcriptional activity, whose modular structure with various binding motifs, allows the formation of multi-protein signaling complexes. This results in the induction and/or maintenance of signaling pathways with pleiotropic effects on cell motility, cell adhesion, cytoskeleton remodeling, invasion, survival, and proliferation. Deregulation of p130Cas/BCAR1 adaptor protein has been extensively demonstrated in a variety of human cancers in which overexpression of p130Cas/BCAR1 correlates with increased malignancy. p140Cap (p130Cas associated protein), encoded by the SRCIN1 gene, has been discovered by affinity chromatography and mass spectrometry analysis of putative interactors of p130Cas. It came out that p140Cap associates with p130Cas not directly but through its interaction with the Src Kinase. p140Cap is highly expressed in neurons and to a lesser extent in epithelial tissues such as the mammary gland. Strikingly, in vivo and in vitro analysis identified its tumor suppressive role in breast cancer and in neuroblastoma, showing an inverse correlation between p140Cap expression in tumors and tumor progression. In this review, a synopsis of 15 years of research on the role of p130Cas/BCAR1 and p140Cap/SRCIN1 in breast cancer will be presented.

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“…p140Cap shares different Intrinsically Disordered Regions (IDRs) that classify p140Cap as "Intrinsic Disorder Protein" (IDP) [30,31]. The IDP features of p140Cap could allow the interaction with several partners and promote protein-protein interactions that are the elected functions for a scaffold protein.…”

Section: The P140cap Adaptor Proteinmentioning

confidence: 99%

“…The IDP features of p140Cap could allow the interaction with several partners and promote protein-protein interactions that are the elected functions for a scaffold protein. The p140Cap protein can interact with multiple partners [30] (Figure 1). In particular, p140Cap associates with the tyrosine kinases Csk and Src.…”

Section: The P140cap Adaptor Proteinmentioning

confidence: 99%

The Scaffold Protein p140Cap as a Molecular Hub for Limiting Cancer Progression: A New Paradigm in Neuroblastoma

Centonze¹,

Chapelle²,

Angelini³

et al. 2021

Pheochromocytoma, Paraganglioma and Neuroblastoma

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Neuroblastoma, the most common extra-cranial pediatric solid tumor, is responsible for 9–15% of all pediatric cancer deaths. Its intrinsic heterogeneity makes it difficult to successfully treat, resulting in overall survival of 50% for half of the patients. Here we analyze the role in neuroblastoma of the adaptor protein p140Cap, encoded by the SRCIN1 gene. RNA-Seq profiles of a large cohort of neuroblastoma patients show that SRCIN1 mRNA levels are an independent risk factor inversely correlated to disease aggressiveness. In high-risk patients, SRCIN1 was frequently altered by hemizygous deletion, copy-neutral loss of heterozygosity, or disruption. Functional assays demonstrated that p140Cap is causal in dampening both Src and Jak2 kinase activation and STAT3 phosphorylation. Moreover, p140Cap expression decreases in vitro migration and anchorage-independent cell growth, and impairs in vivo tumor progression, in terms of tumor volume and number of spontaneous lung metastasis. p140Cap also contributes to an increased sensitivity of neuroblastoma cells to chemotherapy drugs and to the combined usage of doxorubicin and etoposide with Src inhibitors. Overall, we provide the first evidence that SRCIN1/p140Cap is a new independent prognostic marker for patient outcome and treatment, with a causal role in curbing the aggressiveness of neuroblastoma. We highlight the potential clinical impact of SRCIN1/p140Cap expression in neuroblastoma tumors, in terms of reducing cytotoxic effects of chemotherapy, one of the main issues for pediatric tumor treatment.

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The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness

Cited by 7 publications

References 83 publications

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

p130Cas/BCAR1 and p140Cap/SRCIN1 Adaptors: The Yin Yang in Breast Cancer?

The Scaffold Protein p140Cap as a Molecular Hub for Limiting Cancer Progression: A New Paradigm in Neuroblastoma

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