CD73 promotes tumor metastasis by modulating RICS/RhoA signaling and EMT in gastric cancer

Xu, Zhijun; Gu, Chun-Cai; Yao, Xiang; Guo, Weihong; Wang, Huanan; Lin, Tian; Li, Fengping; Chen, Da; Wu, Jianzhong; Ye, Gengtai; Zhao, Liying; Hu, Yanfeng; Yu, Jiang; Shi, Jiaolong; Li, Guoxin; Liu, Hao

doi:10.1038/s41419-020-2403-6

Cited by 66 publications

(57 citation statements)

References 56 publications

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“…Rho/ROCK/LIMK/cofilin is one of the Rho GTPase pathways, the inhibition of Rho/ROCK/LIMK/cofilin pathway resulted in the destroy of F-actin stabilization and redistribution of cytoplasmic actin via inhibition of cofilin phosphorylation, which promoted EMT process as well as gastric cancer metastasis. RICS and PRP4 are two GTPase-activating proteins that directly interacts with Rho, they function as upstream effectors and inhibit phosphorylation of cofilin by inactivate LIMK (Islam et al, 2018 ; Xu et al, 2020 ). However, another cofilin related pathway showed opposite relationship between phosphorylation of cofilin and EMT process.…”

Section: Cofilin In Cancersmentioning

confidence: 99%

Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis

Huang

Zhao

et al. 2021

Front. Cell Dev. Biol.

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Cofilin is an actin-binding protein that regulates filament dynamics and depolymerization. The over-expression of cofilin is observed in various cancers, cofilin promotes cancer metastasis by regulating cytoskeletal reorganization, lamellipodium formation and epithelial-to-mesenchymal transition. Clinical treatment of cancer regarding cofilin has been explored in aspects of tumor cells apoptosis and cofilin related miRNAs. This review addresses the structure and phosphorylation of cofilin and describes recent findings regarding the function of cofilin in regulating cancer metastasis and apoptosis in tumor cells.

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Section: Cofilin In Cancersmentioning

confidence: 99%

Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis

Huang

Zhao

et al. 2021

Front. Cell Dev. Biol.

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“…In cancer, hypoxia induces CD73 expression through hypoxia-inducible factor-1α (HIF-1α) activation and their expressions positively correlate in clinical cancer samples 14 , 25 . Recent studies associated CD73 expression with EMT regulation in cancer 9 , 26 , 27 . The aim of this study was to further investigate the mechanisms how CD73 may contribute to tumor progression.…”

Section: Introductionmentioning

confidence: 99%

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

Petruk

Tuominen

Åkerfelt

et al. 2021

Sci Rep

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CD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition.

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“…ADO signals as well as the activation of its receptor can modulate the EMT in different types of cancer such as head, gastric and lung cancer, resulting in a more invasive phenotype [ 39 , 83 , 84 ]. Accordingly, high ADO concentrations are able to promote the gene expression of Snail and ZEB1, two master gene regulators of GMT induction.…”

Section: Discussionmentioning

confidence: 99%

High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome

Pietrobono

Giacomelli

Marchetti

et al. 2020

IJMS

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Glioblastoma is an aggressive, fast-growing brain tumor influenced by the composition of the tumor microenvironment (TME) in which mesenchymal stromal cell (MSCs) play a pivotal role. Adenosine (ADO), a purinergic signal molecule, can reach up to high micromolar concentrations in TME. The activity of specific adenosine receptor subtypes on glioma cells has been widely explored, as have the effects of MSCs on tumor progression. However, the effects of high levels of ADO on glioma aggressive traits are still unclear as is its role in cancer cells-MSC cross-talk. Herein, we first studied the role of extracellular Adenosine (ADO) on isolated human U343MG cells as a glioblastoma cellular model, finding that at high concentrations it was able to prompt the gene expression of Snail and ZEB1, which regulate the epithelial–mesenchymal transition (EMT) process, even if a complete transition was not reached. These effects were mediated by the induction of ERK1/2 phosphorylation. Additionally, ADO affected isolated bone marrow derived MSCs (BM-MSCs) by modifying the pattern of secreted inflammatory cytokines. Then, the conditioned medium (CM) of BM-MSCs stimulated with ADO and a co-culture system were used to investigate the role of extracellular ADO in GBM–MSC cross-talk. The CM promoted the increase of glioma motility and induced a partial phenotypic change of glioblastoma cells. These effects were maintained when U343MG cells and BM-MSCs were co-cultured. In conclusion, ADO may affect glioma biology directly and through the modulation of the paracrine factors released by MSCs overall promoting a more aggressive phenotype. These results point out the importance to deeply investigate the role of extracellular soluble factors in the glioma cross-talk with other cell types of the TME to better understand its pathological mechanisms.

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CD73 promotes tumor metastasis by modulating RICS/RhoA signaling and EMT in gastric cancer

Cited by 66 publications

References 56 publications

Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis

Cofilin: A Promising Protein Implicated in Cancer Metastasis and Apoptosis

CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

High Adenosine Extracellular Levels Induce Glioblastoma Aggressive Traits Modulating the Mesenchymal Stromal Cell Secretome

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