Upregulated Vav2 in gastric cancer tissues promotes tumor invasion and metastasis

Tan, Bibo; Li, Yong; Fan, Li; Zhao, Qun; Liu, Qingwei; Yu, Li; Wang, Dong; Nan, Jun

doi:10.1177/1010428317698392

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…MMP3 over-expression in CAFs was observed in mammary glands [70], MMP2 is over-expressed in gliomas [71], whereas MMP1 was observed to increase in melanoma [72] and breast cancer [73]. Moreover, CAFs are actively involved in the secretion of proteases, like uPA, which can cleave and activate MMPs [74].…”

Section: Mechanisms Of Caf-mediated Control Of Tumor Progressionmentioning

confidence: 99%

Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance

et al. 2019

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In the last decades, the role of the microenvironment in tumor progression and therapeutic outcome has gained increasing attention. Cancer-associated fibroblasts (CAFs) have emerged as key players among stromal cells, owing to their abundance in most solid tumors and their diverse tumor-restraining/promoting roles. The interplay between tumor cells and neighboring CAFs takes place by both paracrine signals (cytokines, exosomes and metabolites) or by the multifaceted functions of the surrounding extracellular matrix. Here, we dissect the most recent identified mechanisms underlying CAF-mediated control of tumor progression and therapy resistance, which include induction of the epithelial-to-mesenchymal transition (EMT), activation of survival pathways or stemness-related programs and metabolic reprogramming in tumor cells. Importantly, the recently unveiled heterogeneity in CAFs claims tailored therapeutic efforts aimed at eradicating the specific subset facilitating tumor progression, therapy resistance and relapse. However, despite the large amount of pre-clinical data, much effort is still needed to translate CAF-directed anti-cancer strategies from the bench to the clinic.

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Section: Mechanisms Of Caf-mediated Control Of Tumor Progressionmentioning

confidence: 99%

Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance

et al. 2019

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“…Moreover, Vav2/3 overexpression and activation has been reported from multiple cancers, including metastatic melanoma, endometrial, cervical, breast, and prostate cancer (Cook et al, 2014) (Table 1). In gastric cancer, Vav2/3 expression and activities were related to the degree of tumor differentiation, lymph node metastasis, and higher grade invasive and metastatic tumors (Tan et al, 2017a). Vav2 is also activated in papillary thyroid cancer, being phosphorylated through EphB3 tyrosine kinase receptors (Li et al, 2017).…”

Section: Targeting Vav1/2/3mentioning

confidence: 99%

Targeting Rac and Cdc42 GEFs in Metastatic Cancer

Maldonado

Medina

Velázquez

et al. 2020

Front. Cell Dev. Biol.

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The Rho family GTPases Rho, Rac, and Cdc42 have emerged as key players in cancer metastasis, due to their essential roles in regulating cell division and actin cytoskeletal rearrangements; and thus, cell growth, migration/invasion, polarity, and adhesion. This review will focus on the close homologs Rac and Cdc42, which have been established as drivers of metastasis and therapy resistance in multiple cancer types. Rac and Cdc42 are often dysregulated in cancer due to hyperactivation by guanine nucleotide exchange factors (GEFs), belonging to both the diffuse B-cell lymphoma (Dbl) and dedicator of cytokinesis (DOCK) families. Rac/Cdc42 GEFs are activated by a myriad of oncogenic cell surface receptors, such as growth factor receptors, G-protein coupled receptors, cytokine receptors, and integrins; consequently, a number of Rac/Cdc42 GEFs have been implicated in metastatic cancer. Hence, inhibiting GEF-mediated Rac/Cdc42 activation represents a promising strategy for targeted metastatic cancer therapy. Herein, we focus on the role of oncogenic Rac/Cdc42 GEFs and discuss the recent advancements in the development of Rac and Cdc42 GEF-interacting inhibitors as targeted therapy for metastatic cancer, as well as their potential for overcoming cancer therapy resistance.

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“…However, the outcomes are often poor, with 5-year survival less than 10 % globally [2]. The high metastatic nature of the GC contributes to poor prognosis of patients [10]. The pathogenesis of GC involves several signaling pathways and abnormal gene expression patterns which are often accompanied by inactivation of tumor suppressor genes and activation of oncogenes [2].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of gastric cancer cell growth, invasion and metastasis by tocotrienolic amide

Huang¹,

Xu²

2021

Trop. J. Pharm Res

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Purpose: To investigate the effect of tocotrienolic amide on gastric cancer (GC) cell growth and metastasis, and the underlying mechanism of action.Methods: Gastric cancer (GC) cell lines MKN28 and NCI-N87 were cultured in Dulbecco's modified Eagle medium (DMEM) supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin solution at 37 ˚C in a humidified atmosphere of 5 % CO2 and 95 % air. Cell invasion and migration were determined using Transwell and wound healing assays, respectively. Realtime quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used for the determination of changes in the levels of expression of Snail, E-cadherin, vimentin, and microRNA-195-5p (miR-195-5p). In vivo tumor growth inhibition was determined 45 days after establishment of GC xenografts in nude mice.Results: Treatment of MKN28 and NCI-N87 cells with tocotrienolic amide significantly and dosedependently reduced their invasiveness and migratory capacity (p < 0.05). It also significantly and dosedependently downregulated the mRNA and protein expressions of Snail and vimentin, but significantly upregulated E-cadherin expression (p < 0.05). The mRNA expression of miR-195-5p was significantly and dose-dependently upregulated in MKN28 and NCI-N87 cells treated with tocotrienolic amide, but was downregulated after transfection with miR-195-5p inhibitor (p < 0.05). Transfection of MKN28 and NCI-N87 cells with miR-195-5p inhibitor significantly and dose-dependently upregulated mRNA and protein expressions of Snail (p < 0.05). Moreover, treatment of GC mice with TCTA led to significant and dose-dependent reduction in tumor weight and volume (p < 0.05).Conclusion: These results suggest that tocotrienolic amide inhibits the growth and metastasis of GC cells by directly targeting Snail and vimentin genes, and thus can potentially be developed for the management of gastric cancer. Keywords: Gastric cancer, Metastasis, Protein expression, Tocotrienolic amide, Tumor volume

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Upregulated Vav2 in gastric cancer tissues promotes tumor invasion and metastasis

Cited by 11 publications

References 29 publications

Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance

Cancer-associated fibroblasts as abettors of tumor progression at the crossroads of EMT and therapy resistance

Targeting Rac and Cdc42 GEFs in Metastatic Cancer

Inhibition of gastric cancer cell growth, invasion and metastasis by tocotrienolic amide

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