Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin

Jeong, Bo Young; Cho, Kyung Hwa; Jeong, Kang Jin; Park, Yun Yong; Kim, Jin Man; Rha, Sun Young; Park, Chang Gyo; Mills, Gordon B.; Cheong, Jae‐Ho; Lee, Hoi Young

doi:10.1038/emm.2017.248

Cited by 46 publications

(40 citation statements)

References 43 publications

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“…Indeed, treatment with a stapled peptide, which inhibits interactions between Rab25 and its effectors, suppresses the proliferation and migration of ovarian cancer cells in which Rab25 functions as an oncogene, but augments the aggressive phenotype in breast cancer cells in which Rab25 functions as a tumor suppressor . Furthermore, Jeong et al found that the oncogenic activity of Rab25 in ovarian cancer cell lines accrued through Rab25‐dependent increases in β1 integrin levels, which subsequently activated EGFR, upregulated VEGF‐A expression, and increased Snail expression, ultimately promoting cancer cell invasion . These data suggested that while Rab25 regulates trafficking in many cells, the actual patterns of integrin regulation are dependent on tumor context.…”

Section: Discussionmentioning

confidence: 99%

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

Jeong

Lim

Kim

et al. 2019

The Journal of Pathology

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Rab25 can function as both a tumor suppressor and a tumor promoter across different tissues. This study sought to clarify the role of Rab25 as a tumor suppressor in skin squamous cell carcinoma (SCC). Rab25 loss was closely associated with neoplastic transition in both humans and mice. Rab25 loss was well correlated with increased cell proliferation and poor differentiation in human SCC. While Rab25 knockout (KO) in mice did not induce spontaneous tumor formation, it did significantly accelerate tumor generation and promote malignant transformation in a mouse two‐stage skin carcinogenesis model. Xenografting of a Rab25‐deficient human keratinocyte cell line, HaCaT, also elicited neoplastic transformation. Notably, Rab25 deficiency led to dysregulation of integrins β1, β4, and α6, which matched well with increased epidermal proliferation and impaired desmosome–tight junction formation. Rab25 deficiency induced impairment of integrin recycling, leading to the improper expression of integrins. In line with this, significant attenuation of integrin β1, β4, and α6 expression was identified in human SCCs where Rab25 was deficient. Collectively, these results suggest that loss of Rab25 promotes the development and neoplastic transition of SCC through dysregulation of integrin trafficking. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

Jeong

Lim

Kim

et al. 2019

The Journal of Pathology

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“…An important event underlying metastasis is EMT. Extensive literature has established links between transcriptional factors (EMT-TFs) such as Snail1 [ 107 , 108 ], ZEB [ 109 ], Twist [ 110 , 111 ] and metastatic processes of cancer cells e.g. E-cadherin downregulation, angiogenesis, and intravasation [ 107 ].…”

Section: Stromal Metamorphosis and Metastasis: A Story Of Reciprocitymentioning

confidence: 99%

Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review

Emon

Bauer

Jain

et al. 2018

Computational and Structural Biotechnology Journal

206

178

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The role of tumor microenvironment in cancer progression is gaining significant attention. It is realized that cancer cells and the corresponding stroma co-evolve with time. Cancer cells recruit and transform the stromal cells, which in turn remodel the extra cellular matrix of the stroma. This complex interaction between the stroma and the cancer cells results in a dynamic feed-forward/feed-back loop with biochemical and biophysical cues that assist metastatic transition of the cancer cells. Although biochemistry has long been studied for the understanding of cancer progression, biophysical signaling is emerging as a critical paradigm determining cancer metastasis. In this mini review, we discuss the role of one of the biophysical cues, mostly the mechanical stiffness of tumor microenvironment, in cancer progression and its clinical implications.

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“…The effect of AGPS on the pathway network was analyzed in human glioma cells by sequencing and bioinformatics analysis, and it was discovered that AGPS silencing regulated tumor-related signaling pathways, such as the PI3K/Akt, Toll-like receptor, focal adhesion and VEGF signaling pathways. These aforementioned results were further validated by RT-qPCR, where significantly upregulated expression levels of THBS1 and ITGA11, and downregulated expression levels of SPP1, VEGFA, EGFR, IL7R, CXCL8, PTGS2 and SDC4, were all identified; all of these are crucial genes involved in the aforementioned signaling pathways, and have been found to serve roles in tumor metastasis and angiogenesis (18)(19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 72%

Effect of alkylglycerone phosphate synthase on the expression levels of lncRNAs in glioma cells and its functional prediction

Chen

Zhang

et al. 2020

Oncol Lett

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Alkylglycerone phosphate synthase (AGPS) is a key enzyme for ether ester synthesis and acts as an oncogene in malignant tumors. The present study aimed to investigate the effect of AGPS silencing on the expression levels of long non-coding RNAs (lncRNAs) and the co-expression with mRNAs in glioma U251 cells using microarray analysis. Furthermore, the underlying biological functions of crucial lncRNAs identified were investigated. It was discovered that in vitro U251 cell proliferation was suppressed following the genetic silencing of AGPS. Differentially expressed lncRNAs and mRNAs in U251 cells were sequenced following AGPS silencing. The results from the Gene Ontology analysis identified that the co-expressed mRNAs were mainly involved in biological processes, such as 'cellular response to hypoxia', 'extracellular matrix organization' and 'PERK-mediated unfolded protein response'. In addition, Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis revealed that the co-expressed mRNAs were the most enriched in the 'AGE/RAGE signaling pathway in diabetic conditions'. Additionally, the PI3K/Akt and epidermal growth factor receptor signaling pathways serve important roles in tumor processes, for example carcinogenesis and angiogenesis. Furthermore, it was identified that the lncRNA AK093732 served a vital role in the regulatory network and the core pathway in this network regulated by this lncRNA was discovered to be the 'Cytokine-cytokine receptor interaction'. In conclusion, the findings of the present study suggested that AGPS may affect cell proliferation and the degree of malignancy. In addition, the identified lncRNAs and their co-expressed mRNAs screened using microarrays may have significant biological effects in the occurrence, development and metastasis of glioma, and thus may be novel markers of glioma.

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Rab25 augments cancer cell invasiveness through a β1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin

Cited by 46 publications

References 43 publications

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review

Effect of alkylglycerone phosphate synthase on the expression levels of lncRNAs in glioma cells and its functional prediction

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