Arf proteins in cancer cell migration

Casalou, Cristina; Faustino, Alexandra; Barral, Duarte C.

doi:10.1080/21541248.2016.1228792

Cited by 61 publications

(52 citation statements)

References 133 publications

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“…Cancer cell migration requires coordinated assembly and disassembly of cell-ECM contacts, mediated by FAs. Indeed, several ARF GAPs, namely ASAP1, ASAP2, GIT1 and GIT2 have been found to be localized at FAs (Casalou et al, 2016). GIT1, which inactivates ARF6 specifically, is highly expressed in several types of cancers, including breast, cervical, colon and liver (Yoo et al, 2012;Chan et al, 2014;Huang et al, 2014;Peng et al, 2014).…”

Section: Arf Gefs and Gapsmentioning

confidence: 99%

The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

Casalou

Ferreira

Barral

2020

Front. Cell Dev. Biol.

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The Adenosine diphosphate-Ribosylation Factor (ARF) family belongs to the RAS superfamily of small GTPases and is involved in a wide variety of physiological processes, such as cell proliferation, motility and differentiation by regulating membrane traffic and associating with the cytoskeleton. Like other members of the RAS superfamily, ARF family proteins are activated by Guanine nucleotide Exchange Factors (GEFs) and inactivated by GTPase-Activating Proteins (GAPs). When active, they bind effectors, which mediate downstream functions. Several studies have reported that cancer cells are able to subvert membrane traffic regulators to enhance migration and invasion. Indeed, members of the ARF family, including ARF-Like (ARL) proteins have been implicated in tumorigenesis and progression of several types of cancer. Here, we review the role of ARF family members, their GEFs/GAPs and effectors in tumorigenesis and cancer progression, highlighting the ones that can have a pro-oncogenic behavior or function as tumor suppressors. Moreover, we propose possible mechanisms and approaches to target these proteins, toward the development of novel therapeutic strategies to impair tumor progression.

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Section: Arf Gefs and Gapsmentioning

confidence: 99%

The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

Casalou

Ferreira

Barral

2020

Front. Cell Dev. Biol.

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“…As other Arf GAP family members, AGAP2 can be also regulated through other mechanisms such as membrane interaction/association via PH domain or protein-protein interaction via ANK repeats [16]. AGAP2 also interacts with Arf proteins and exhibits high affinity for Arf1, Arf5 and Arf6 substrates, in decreasing order of affinity [17].…”

Section: Two Human Agap2 Isoforms: Pike-l and Agap2mentioning

confidence: 99%

AGAP2: Modulating TGFβ1-Signaling in the Regulation of Liver Fibrosis

Navarro‐Corcuera

Ansorena

Montiel-Duarte

et al. 2020

IJMS

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AGAP2 (Arf GAP with GTP-binding protein-like domain, Ankyrin repeat and PH domain 2) isoform 2 is a protein that belongs to the Arf GAP (GTPase activating protein) protein family. These proteins act as GTPase switches for Arfs, which are Ras superfamily members, being therefore involved in signaling regulation. Arf GAP proteins have been shown to participate in several cellular functions including membrane trafficking and actin cytoskeleton remodeling. AGAP2 is a multi-tasking Arf GAP that also presents GTPase activity and is involved in several signaling pathways related with apoptosis, cell survival, migration, and receptor trafficking. The increase of AGAP2 levels is associated with pathologies as cancer and fibrosis. Transforming growth factor beta-1 (TGF-β1) is the most potent pro-fibrotic cytokine identified to date, currently accepted as the principal mediator of the fibrotic response in liver, lung, and kidney. Recent literature has described that the expression of AGAP2 modulates some of the pro-fibrotic effects described for TGF-β1 in the liver. The present review is focused on the interrelated molecular effects between AGAP2 and TGFβ1 expression, presenting AGAP2 as a new player in the signaling of this pro-fibrotic cytokine, thereby contributing to the progression of hepatic fibrosis.

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“…The ADP-ribosylation factor 1 (ARF1) has been reported as significantly elevated in various cancers [41], and its expression in prostate cancer correlated with activation of ERK1 and ERK2, leading to cell proliferation [42]. We found ARF1 to be significantly higher in the WT tumor proteome (ARF1↑WT; no peptides/PSM in G12V vs. 10 peptides and 137 PSM in WT), which might represent an EGFR-independent activation of the RAS/MEK/ERK pathway and a potential escape mechanism for anti-EGFR therapy.…”

Section: Quantitative Comparison Of Kras G12v and Kras Wt Tumorsmentioning

confidence: 99%

Proteogenomics of Colorectal Cancer Liver Metastases: Complementing Precision Oncology with Phenotypic Data

Blank-Landeshammer

Richard

Mitsa

et al. 2019

Cancers

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Hotspot testing for activating KRAS mutations is used in precision oncology to select colorectal cancer (CRC) patients who are eligible for anti-EGFR treatment. However, even for KRAS wildtype tumors anti-EGFR response rates are <30%, while mutated-KRAS does not entirely rule out response, indicating the need for improved patient stratification. We performed proteogenomic phenotyping of KRAS wildtype and KRAS G12V CRC liver metastases (mCRC). Among >9000 proteins we detected considerable expression changes including numerous proteins involved in progression and resistance in CRC. We identified peptides representing a number of predicted somatic mutations, including KRAS G12V . For eight of these, we developed a multiplexed parallel reaction monitoring (PRM) mass spectrometry assay to precisely quantify the mutated and canonical protein variants. This allowed phenotyping of eight mCRC tumors and six paired healthy tissues, by determining mutation rates on the protein level. Total KRAS expression varied between tumors (0.47-1.01 fmol/µg total protein) and healthy tissues (0.13-0.64 fmol/µg). In KRAS G12V -mCRC, G12V-mutation levels were 42-100%, while one patient had only 10% KRAS G12V but 90% KRAS wildtype . This might represent a missed therapeutic opportunity: based on hotspot sequencing, the patient was excluded from anti-EGFR treatment and instead received chemotherapy, while PRM-based tumor-phenotyping indicates the patient might have benefitted from anti-EGFR therapy.

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Arf proteins in cancer cell migration

Cited by 61 publications

References 133 publications

The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

The Role of ARF Family Proteins and Their Regulators and Effectors in Cancer Progression: A Therapeutic Perspective

AGAP2: Modulating TGFβ1-Signaling in the Regulation of Liver Fibrosis

Proteogenomics of Colorectal Cancer Liver Metastases: Complementing Precision Oncology with Phenotypic Data

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