A Novel Sialyltransferase Inhibitor Suppresses FAK/Paxillin Signaling and Cancer Angiogenesis and Metastasis Pathways

Chen, Jia Yang; Tang, Yen An; Huang, Sin Ming; Juan, Hsueh‐Fen; Wu, Li-Wha; Sun, Ying; Wang, Szu Chi; Wu, Kuan Wei; Balraj, Gopula; Chang, Tzu Ting; Li, Wen‐Shan; Cheng, Hsiu Chi; Wang, Yi‐Ching

doi:10.1158/0008-5472.can-10-1303

Cited by 114 publications

(93 citation statements)

References 40 publications

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“…The increased ␣2,6-linked sialylation on ␤1-integrins also has been reported in several transformed cell types and is postulated to alter integrin function by enhancing its activation state and binding to collagen (17)(18)(19). In these studies, increases in ␣2,6-linked sialylation levels have been correlated with enhanced cell motility and invasiveness in vitro.…”

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confidence: 73%

An Oncogenic Protein Golgi Phosphoprotein 3 Up-regulates Cell Migration via Sialylation

Isaji

et al. 2014

Journal of Biological Chemistry

133

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Background: Molecular mechanisms of the effect of the GOLPH3 oncogenic protein on tumorigenesis remain unclear. Results: GOLPH3 specifically up-regulates sialylation of integrin N-glycans, promotes sialylation-dependent cell migration, and affects AKT signaling. Conclusion: GOLPH3 affects cell biological functions through a specific regulation of sialylation. Significance: The sialylation of N-glycans is important for functions of GOLPH3.

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mentioning

confidence: 73%

An Oncogenic Protein Golgi Phosphoprotein 3 Up-regulates Cell Migration via Sialylation

Isaji

et al. 2014

Journal of Biological Chemistry

133

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“…For example, inhibition of paxillin phosphorylation by the sialytransferase inhibitor Lith-O-Asp or other small molecules suppress lung tumor progression and metastasis (Chen et al, 2011;Huang et al, 2012), as well as breast cancer progression (Golubovskaya et al, 2008), in vivo. Interestingly, these molecules affect phosphorylation activity in the N-terminal region of paxillin, and we have shown here and in a previous study that the expression of the N-terminal alone substantially increases migration when transfected into paxillin knockdown cells, where N-terminus and C-terminus of paxillin have been shown to have complementary but opposite effects on cell migration and invasion (Sero et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Paxillin controls endothelial cell migration and tumor angiogenesis by altering neuropilin 2 expression

German

Mammoto

Jiang

et al. 2014

Journal of Cell Science

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Although a number of growth factors and receptors are known to control tumor angiogenesis, relatively little is known about the mechanism by which these factors influence the directional endothelial cell migration required for cancer microvessel formation. Recently, it has been shown that the focal adhesion protein paxillin is required for directional migration of fibroblasts in vitro. Here, we show that paxillin knockdown enhances endothelial cell migration in vitro and stimulates angiogenesis during normal development and in response to tumor angiogenic factors in vivo. Paxillin produces these effects by decreasing expression of neuropilin 2 (NRP2). Moreover, soluble factors secreted by tumors that stimulate vascular ingrowth, including vascular endothelial growth factor (VEGF), also decrease endothelial cell expression of paxillin and NRP2, and overexpression of NRP2 reverses these effects. These results suggest that the VEGF-paxillin-NRP2 pathway could represent a new therapeutic target for cancer and other angiogenesis-related diseases.

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“…Paxillin and FAK are two key signaling molecules in integrin-mediated signaling pathways and are closely associated with cell adhesion, tumor cell migration, cell proliferation and cell survival (8)(9)(10)(11). Some studies have shown that FAK plays a significant role in the integrin signaling pathway (12).…”

Section: Discussionmentioning

confidence: 99%

Expression of paxillin and FAK mRNA and the related clinical significance in esophageal carcinoma

et al. 2011

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Abstract. The objective of the present study was to investigate the expression of paxillin and focal adhesion kinase (FAK) mRNA in esophageal carcinoma tissues, and their relationship with clinicopathological parameters, as well as to analyze the correlation of paxillin and FAK mRNA levels in esophageal carcinoma. By using reverse transcription polymerase chain reaction (RT-PCR), the mRNA expression levels of paxillin and FAK were detected in 121 samples of esophageal carcinoma, 43 samples of atypical hyperplasia and 56 samples of normal esophageal mucosa. The results showed that the positive rates of paxillin and FAK mRNA expression in esophageal carcinoma were 87.6 and 80.17%, respectively, which were significantly higher (P<0.05) than those in atypical hyperplasia (44.19 and 39.53%) and normal esophageal mucosa (5.36 and 12.5%). Notably, paxillin and FAK mRNA expression levels were significantly correlated with the differentiation degree and depth of invasion of esophageal carcinoma and with lymph node metastasis (P<0.05). In addition, paxillin and FAK mRNA expression levels in esophageal carcinoma were positively correlated (r=0.4804, P=0.000).In conclusion, the combined detection of paxillin and FAK mRNA expression is expected to provide a theoretical basis for the molecular diagnosis of esophageal carcinoma. IntroductionPaxillin is a tyrosine kinase substrate and a significant cell adhesion molecule. Paxillin is associated with integrin and its related cellular and extracellular matrix molecules. As such, paxillin helps to regulate cell migration, dissemination and other functions, and enhances tumor cell invasion and metastasis (1,2). Focal adhesion kinase (FAK) is distributed in the cellular focal adhesion sites and plays a crucial role in the regulation of tumor cell migration (3,4). Thus, paxillin and FAK are both related to the occurrence of tumors and their biological behavior. In this study, reverse transcription polymerase chain reaction (RT-PCR) was used to detect paxillin and FAK mRNA expression in esophageal carcinoma, atypical dysplasia and normal esophageal mucosa. This study also investigated the relationship of paxillin, FAK and clinicopathological parameters, as well as the correlation between paxillin and FAK expression, in order to provide a theoretical basis for a molecular diagnostic for esophageal carcinoma. Materials and methodsGeneral information. Fresh specimens were collected from esophagectomies of 121 patients while visiting the Department of Oncology, Affiliated Hospital, Xuzhou Medical College (Jiangsu Province, China) from March 1, 2010 to March 1, 2011. Subjects included 68 males and 53 females, aged 35 to 80 years; all had no preoperative chemotherapy, radiotherapy or immunotherapy history. Shortly following specimen harvest, two samples were taken from each of three sites -necrosis-free carcinoma (within 3 cm of the expected carcinoma) and distant, normal mucosa. For each tissue, one of the two samples was stored in liquid nitrogen for later RT-PCR preparation. The second s...

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A Novel Sialyltransferase Inhibitor Suppresses FAK/Paxillin Signaling and Cancer Angiogenesis and Metastasis Pathways

Cited by 114 publications

References 40 publications

An Oncogenic Protein Golgi Phosphoprotein 3 Up-regulates Cell Migration via Sialylation

An Oncogenic Protein Golgi Phosphoprotein 3 Up-regulates Cell Migration via Sialylation

Paxillin controls endothelial cell migration and tumor angiogenesis by altering neuropilin 2 expression

Expression of paxillin and FAK mRNA and the related clinical significance in esophageal carcinoma

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