Clinical and Prognostic Significance of RhoA and RhoC Gene Expression in Esophageal Squamous Cell Carcinoma

Faried, Ahmad; Faried, Leri S.; Usman, Nurhayat; Kato, Hiroyuki; Kuwano, Hiroyuki

doi:10.1245/s10434-007-9562-x

Cited by 51 publications

(40 citation statements)

References 29 publications

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“…Enhanced RhoA activity in the cancer cells is mostly due to RhoA overexpression because mutation of RhoA has not been found in human cancers (33,34). Accumulating evidences have shown that upregulation of RhoA mRNA and RhoA protein levels has been well documented in various human cancers (29,30,35). The present study suggests one potent mechanism of epithelial RhoA overexpression via wound-induced NAG-1.…”

Section: Discussionsupporting

confidence: 58%

“…In contrast, the current study observed elevation of total level of RhoA protein. Upregulation of RhoA expression has been also observed in various types of human cancer cells (29)(30)(31), and one suggested deciphering of the oncogenic induction of RhoA expression is the signaling orchestration by Myc-Skp2-Miz1-p300 transcriptional complex (32). Enhanced RhoA activity in the cancer cells is mostly due to RhoA overexpression because mutation of RhoA has not been found in human cancers (33,34).…”

Section: Discussionmentioning

confidence: 99%

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Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug–Activated Gene 1 Counteracts Intestinal Ulcerative Injuries

Choi

Hun

Park

et al. 2016

The Journal of Immunology

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In response to ulcerative mucosal injuries, intestinal epithelial restitution is a critical event in the early defense against harmful attacks by luminal Ags. Based on the assumption that epithelial NAG-1 is an endogenous regulator of ulcerative stress-induced injuries, the expression and functions of NAG-1 were investigated. Genetic ablation of NAG-1 decreased survival of mice with dextran sodium sulfate–induced intestinal ulcer and histologically delayed the epithelial restitution, confirming early protective roles of NAG-1 in ulcerative insults. Moreover, enhanced expression of NAG-1 during the wound-healing process was associated with epithelial cell migration and spreading. In response to ulcerative injury, RhoA GTPase, a cytoskeleton modulator, mediated epithelial restitution via enhanced motility. RhoA expression was prominently elevated in the restituting epithelia cells around the insulted wound bed and was attenuated by NAG-1 deficiency. Pharmacological intervention with RhoA thus attenuated NAG-1–mediated epithelial cell migration during epithelial restitution. Taken together, epithelial restitution was promoted by enhanced NAG-1 expression and subsequent enterocyte locomotion during the early wound-healing process, suggesting clinical usefulness of NAG-1 as a novel endogenous muco-protective factor or an indicator of therapeutic efficacy against the ulcerative gastrointestinal diseases, including inflammatory bowel disease.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug–Activated Gene 1 Counteracts Intestinal Ulcerative Injuries

Choi

Hun

Park

et al. 2016

The Journal of Immunology

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“…Rho has been linked to increased cell proliferation in many cancers, in which it is increased in both amount and activation state (Faried et al, 2007;Sterpetti et al, 2006;Wang, H. B. et al, 2009;Zhang et al, 2009). Mammary carcinoma cells proliferate in response to stiff matrices, and this was shown to be mediated in part by Rho (Paszek et al, 2005;Provenzano et al, 2009;Wozniak et al, 2003).…”

Section: Journal Of Cell Sciencementioning

confidence: 99%

Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling

Provenzano

Keely

2011

Journal of Cell Science

449

379

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SummaryThe notion that cell shape and spreading can regulate cell proliferation has evolved over several years, but only recently has this been linked to forces from within and upon the cell. This emerging area of mechanical signaling is proving to be wide-spread and important for all cell types. The microenvironment that surrounds cells provides a complex spectrum of different, simultaneously active, biochemical, structural and mechanical stimuli. In this milieu, cells probe the stiffness of their microenvironment by pulling on the extracellular matrix (ECM) and/or adjacent cells. This process is dependent on transcellular cell-ECM or cell-cell adhesions, as well as cell contractility mediated by Rho GTPases, to provide a functional linkage through which forces are transmitted through the cytoskeleton by intracellular force-generating proteins. This Commentary covers recent advances in the underlying mechanisms that control cell proliferation by mechanical signaling, with an emphasis on the role of 3D microenvironments and in vivo extracellular matrices. Moreover, as there is much recent interest in the tumor-stromal interaction, we will pay particular attention to exciting new data describing the role of mechanical signaling in the progression of breast cancer. Journal of Cell Sciencephysiological conditions, a dynamic force balance -termed tensional homeostasis -occurs between the cell and the microenvironment, and the cell will proliferate at normal levels (Klein et al., 2009). By contrast, if matrix stiffness is uncharacteristically elevated, an abnormally elevated tensional homeostasis arises that can result in aberrant cellular behaviors. For example, increased matrix stiffness associated with the increased deposition, altered composition and alignment of the collagenous stroma that accompanies breast tumor progression can promote disruption of epithelial architecture (Paszek et al., 2005;Provenzano et al., 2008a;Wozniak et al., 2003). Cells in this environment hyperactivate a mechanically regulated signaling loop that results in increased expression of a conserved set of carcinomaassociated proliferation genes, such as genes that encode cyclins, aurora kinases, cell division cycle regulators and E2F transcription factors, which are important for cell proliferation (Provenzano et al., 2009). Hence, in addition to the cellular microenvironment being an intricate system that includes a complex chemical milieu surrounding the cell, it is now clear that the stiffness of the ECM and the corresponding mechanical response of the cell have a role in regulating fundamental processes -including cell proliferation.In this Commentary, we will cover recent advances in our understanding of the regulation of cell proliferation by mechanical signaling. The emphasis is on the role of mechanical signal transduction in the context of 3D microenvironments, which include cell culture models of defined ECM composition and concentration, such as collagen matrices that contain individual cells or cell communities, models of com...

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“…RhoA and RhoC have been extensively documented for migration and invasion (Faried et al, 2007;Liu et al, 2012;Struckhoff et al, 2011). RhoA expression is increased in human breast cancers due to miRNAmiR-31 suppression, and metastasis in mouse models has also been reported (Valastyan et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of invasion and metastasis of human liver cancer HCCLM3 cells by portulacerebroside A

Qian¹,

Zheng²,

Chen³

et al. 2014

Pharmaceutical Biology

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Objective: This study investigates the effects of PCA in human liver cancer HCCLM3 cells on metastasis and invasion. Materials and methods: After the cells were treated with PCA (2.5, 5, and 10 mg/ml) for 6, 12, 24, or 48 h, adhesion, transwell invasion, and scratch tests were conducted and cell functions were evaluated. Western blot and FQ-RT-PCR assays explored the mechanism of PCA-inhibited invasion and metastasis in the cells. Results:The adhesion rate of the cells was suppressed at 0.5 h (79.4 ± 1.0, 68.7 ± 1.3, and 58.1 ± 1.3%, versus 100 ± 1.5% in the control), 1 h (78.2 ± 1.2, 70.9 ± 1.6, and 55.4 ± 1.9%, versus 100 ± 1.2% in the control), and 1.5 h (71.6 ± 1.1, 62.3 ± 0.9, and 50.4 ± 0.9%, versus 100 ± 1.1% in the control). The 24 h invasion ability was decreased (356.6 ± 11.2, 204.0 ± 17.6, and 113.0 ± 9.5%, versus 443.6 ± 15.4% in the control). The migration capability was also restrained by PCA for 24 h (324.8 ± 25.4, 250.4 ± 21.0, and 126.3 ± 10.1, versus 381.6 ± 30.6 in the control) and 48 h (470.3 ± 34.3, 404.0 ± 19.7, and 201.0 ± 15.4, versus 752.0 ± 63.6 in the control). There was an increase in the mRNA and protein expression levels of TIMP-2 and nm23-H1, inhibition in the mRNA expression of MTA1, MMP-2, and MMP-9, and suppression in the protein expression of MTA1, RhoA, Rac1/Cdc42, MMP-2, but not RhoC and MMP-9. Conclusion: PCA suppresses the invasion and metastasis of HCCLM3 cells possibly by modulation of the mRNA and protein expression of related parameters. This is the first study to reveal a new potential therapeutic application of PCA in antimetastatic therapy for liver cancer.

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Clinical and Prognostic Significance of RhoA and RhoC Gene Expression in Esophageal Squamous Cell Carcinoma

Cited by 51 publications

References 29 publications

Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug–Activated Gene 1 Counteracts Intestinal Ulcerative Injuries

Early Epithelial Restitution by Nonsteroidal Anti-Inflammatory Drug–Activated Gene 1 Counteracts Intestinal Ulcerative Injuries

Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling

Inhibition of invasion and metastasis of human liver cancer HCCLM3 cells by portulacerebroside A

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