Late endosomal and lysosomal trafficking during integrin‐mediated cell migration and invasion

Rainero, Elena; Norman, Jim C.

doi:10.1002/bies.201200160

Cited by 49 publications

(28 citation statements)

References 80 publications

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“…Receptors are normally internalised into the endosomal/lysosomal compartment, when they can be either degraded or spared from degradation and returned to the cell surface [60].…”

Section: Resultsmentioning

confidence: 99%

FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells

Macagno

Díaz-Vera

et al. 2014

PLoS Genet

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Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours.

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“…Receptors are normally internalised into the endosomal/lysosomal compartment, when they can be either degraded or spared from degradation and returned to the cell surface [60].…”

Section: Resultsmentioning

confidence: 99%

FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells

Macagno

Díaz-Vera

et al. 2014

PLoS Genet

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“…ITGαv is over-expressed in human GC tissue and is associated with the five year survival rate of GC patients [28]. Additionally, studies have indicated that ITGαv affects lymph node metastasis and the formation of MMP-9, which could directly provide the driving force for cell migration, especially the migration of cancer cells through endocytosis exocytosis cycle [29, 30]. Combined with the down-regulation of ITGαv in our study, we speculate that this could lead to the decrease in invasion and metastasis of GC cells.…”

Section: Discussionmentioning

confidence: 99%

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

Mao

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chloride intracellular channel 1 (CLIC1), which is a member of the chloride channel protein family, is associated with various human tumors. Recent studies have shown that CLIC1 is involved in the occurrence and development of gastric cancer (GC). However, the exact mechanism remains unclear in GC. Methods: Effects of CLIC1 on the progression of GC in vivo and in vitro and the potential underlying mechanisms have been investigated by analysing 54 patients with GC, as well as human gastric cell lines SGC-7901 and MGC-803, utilizing proteomics, RT-PCR, Western blotting, flow cytometry, Cell invasion and migration assays and xenograft tumor models. Results: Our study shows that CLIC1 knockdown by targeted-siRNA markedly inhibits GC cell invasion and migration and induces apoptosis in vitro. In total, 54 differentially expressed proteins were identified in GC cells SGC-7901 after CLIC1 silencing by isobaric tags for relative isotope labeled and absolute quantitation (iTRAQ) technology, including integrin α1 (ITGα1) and ITGα3. The expression levels of ITGα3, ITGαv, ITGβ1 and Bcl-2 mRNA and protein were decreased significantly in GC cells after CLIC1 knockdown; ITGα1 and Fas were upregulated, but the level of survivin was not significantly different. GC growth and metabolism were decreased in vivo after CLIC1 silencing, but apoptosis was markedly increased. Further study showed that the expression levels of ITGα3, ITGαv and ITGβ1, as well as AKT-phosphorylation, ERK-phosphorylation and p38-phosphorylation, were reduced in vivo after CLIC1 knockdown, while ITGα1 was upregulated. Conclusions: We speculate that CLIC1 may play an important role in the progression of GC, and its mechanism may be related to the regulation of integrin family proteins, which leads to the sequential regulation of the PI3K/AKT, MAPK/ERK and MAPK/p38 pathways.

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“…The contribution made by Rab GTPases to acquisition of invasive behaviour has been intensively studied, and the molecular machinery that is responsible for trafficking receptors that control cell adhesion and cell migration is becoming well understood (Miller et al, 2000; Rainero and Norman, 2013). There is good evidence that Rab11 GTPase control of integrin and receptor tyrosine kinase (RTK) recycling drives invasive migration in cancer, and expression of Rab11 isoforms and their effectors, such as Rab-coupling protein (RCP), is linked to metastasis (Caswell et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

A proteomic approach to identify endosomal cargoes controlling cancer invasiveness

Díaz-Vera

Palmer

Hernández-Fernaud

et al. 2017

Journal of Cell Science

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We have previously shown that Rab17, a small GTPase associated with epithelial polarity, is specifically suppressed by ERK2 (also known as MAPK1) signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this, are unknown. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to a highly selective reduction in the cellular levels of a v-SNARE (Vamp8). Moreover, proteomics and immunofluorescence indicate that Vamp8 is associated with Rab17 at late endosomes. Reduced levels of Vamp8 promote transition between ductal carcinoma in situ (DCIS) and a more invasive phenotype. We developed an unbiased proteomic approach to elucidate the complement of receptors that redistributes between endosomes and the plasma membrane, and have pin-pointed neuropilin-2 (NRP2) as a key pro-invasive cargo of Rab17- and Vamp8-regulated trafficking. Indeed, reduced Rab17 or Vamp8 levels lead to increased mobilisation of NRP2-containing late endosomes and upregulated cell surface expression of NRP2. Finally, we show that NRP2 is required for the basement membrane disruption that accompanies the transition between DCIS and a more invasive phenotype.

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Late endosomal and lysosomal trafficking during integrin‐mediated cell migration and invasion

Cited by 49 publications

References 80 publications

FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells

FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells

CLIC1 Promotes the Progression of Gastric Cancer by Regulating the MAPK/AKT Pathways

A proteomic approach to identify endosomal cargoes controlling cancer invasiveness

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