Integrin α5 triggers the metastatic potential in renal cell carcinoma

Breuksch, Ines; Prosinger, Franz; Baehr, Fabian; Engelhardt, F.; Bauer, Horst; Thüroff, Joachim W.; Heimes, Anne‐Sophie; Hasenburg, Annette; Prawitt, Dirk; Brenner, Walburgis

doi:10.18632/oncotarget.22501

Cited by 16 publications

(18 citation statements)

References 46 publications

(54 reference statements)

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“…Our results are consistent with previous reports that a higher expression level of α5 integrin or increased trafficking to the plasma membrane increases cell attachment and migration (Wan et al. , 2014; Breuksch et al. , 2017).…”

Section: Discussionsupporting

confidence: 93%

GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin

Ahat

Xiang

Zhang

et al. 2019

MBoC

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The Golgi apparatus is a membrane-bound organelle that serves as the center for trafficking and processing of proteins and lipids. To perform these functions, the Golgi forms a multilayer stacked structure held by GRASP55 and GRASP65 trans-oligomers and perhaps their binding partners. Depletion of GRASP proteins disrupts Golgi stack formation and impairs critical functions of the Golgi, such as accurate protein glycosylation and sorting. However, how Golgi destruction affects other cellular activities is so far unknown. Here, we report that depletion of GRASP proteins reduces cell attachment and migration. Interestingly, GRASP depletion reduces the protein level of α5β1 integrin, the major cell adhesion molecule at the surface of HeLa and MDA-MB-231 cells, due to decreased integrin protein synthesis. GRASP depletion also increases cell growth and total protein synthesis. These new findings enrich our understanding on the role of the Golgi in cell physiology and provide a potential target for treating protein-trafficking disorders.

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Section: Discussionsupporting

confidence: 93%

GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin

Ahat

Xiang

Zhang

et al. 2019

MBoC

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“…Experiments were performed in quadruplicates. From the results a mean value and a standard error were calculated [ 46 ].…”

Section: Methodsmentioning

confidence: 99%

Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma

et al. 2018

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Bone metastasis is an important prognostic factor in renal cell carcinoma (RCC). The calcium-sensing receptor (CaSR) has been associated with bone metastasis in several different malignancies. We analyzed the impact of CaSR in bone metastasis in RCC in vitro and in vivo. The RCC cell line 786-O was stably transfected with the CaSR gene and treated with calcium alone or in combination with the CaSR antagonist NPS2143. Afterwards migration, adhesion, proliferation and prominent signaling molecules were analyzed. Calcium treated CaSR-transfected 768-O cells showed an increased adhesion to endothelial cells and the extracellular matrix components fibronectin and collagen I, but not to collagen IV. The chemotactic cell migration and proliferation was also induced by calcium. The activity of SHC, AKT, ERK, P90RSK and JNK were enhanced after calcium treatment of CaSR-transfected cells. These effects were abolished by NPS2143. Development of bone metastasis was evaluated in vivo in a mouse model. Intracardiac injection of CaSR-transfected 768-O cells showed an increased rate of bone metastasis. The results indicate CaSR as an important component in the mechanism of bone metastasis in RCC. Therefore, targeting CaSR might be beneficial in patients with bone metastatic RCC with a high CaSR expression.

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“…For cell adhesion assay amine-binding, maleic anhydride activated clear 96-well-plates (Pierce #15110, Thermo Scientific) were used as described previously [ 20 ]. Extracellular matrix components used were fibronectin (10 μg/ml), vitronectin (5 μg/ml), laminin (50 μg/ml), collagen I (10 μg/ml), collagen IV (10 μg/ml) and as control BSA (10 μg/ml) (all Thermo Scientific).…”

Section: Methodsmentioning

confidence: 99%

In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself

et al. 2018

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BackgroundLoss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression.MethodsIn specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro.ResultsPatients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown.ConclusionsWe could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0247-9) contains supplementary material, which is available to authorized users.

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Integrin α5 triggers the metastatic potential in renal cell carcinoma

Cited by 16 publications

References 46 publications

GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin

GRASP depletion–mediated Golgi destruction decreases cell adhesion and migration via the reduction of α5β1 integrin

Calcium-sensing receptor (CaSR) promotes development of bone metastasis in renal cell carcinoma

In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself

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