XB130, a Novel Adaptor Protein for Signal Transduction

Xu, Jing; Bai, Xiaohui; Lodyga, Monika; Han, Bing; Xiao, Helan; Keshavjee, Shaf; Hu, Jim; Zhang, Haibo; Yang, Burton B.; Liu, Mingyao

doi:10.1074/jbc.m701684200

Cited by 77 publications

(177 citation statements)

References 54 publications

(85 reference statements)

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“…Down-regulation of en-dogenous XB130 with small interfering RNA (siRNA) reduced c-Src activity, IL-8 production, and phosphorylation of Akt in human lung epithelial cells. 9 Our recent study revealed expression of XB130 in human thyroid tissue, and we found that XB130 is a downstream mediator of the signaling cascade propagated by RET/PTC, a genetically rearranged, constitutively active, thyroid-cancer-specific tyrosine kinase. 10 RET/PTC plays a pathogenic role and exhibits transforming ability by exerting its effects on differentiation and on mitogenic and metastatic potential in papillary thyroid cancer.…”

mentioning

confidence: 67%

“…The C-terminal region contains a coiled-coil domain, which might be involved in protein oligomerization and DNA binding. 9 Our studies have implicated XB130 as a likely substrate and regulator of tyrosine kinase-mediated signaling. Down-regulation of en-dogenous XB130 with small interfering RNA (siRNA) reduced c-Src activity, IL-8 production, and phosphorylation of Akt in human lung epithelial cells.…”

mentioning

confidence: 81%

“…9 Antibody for GAPDH came from Santa Cruz Biotechnology (Santa Cruz, CA). Anti-PCNA antibody came from Abcam (Cambridge, MA).…”

Section: Cell Lines Antibodies and Other Reagentsmentioning

confidence: 99%

“…9,10 Cells were transfected with 50 nmol/L pooled XB130 siRNAs using the oligofectamine reagent (Invitrogen, San Diego, CA), as described previously. 9,10,14 The medium containing siRNA was replaced with fresh medium after 24 hours. The siSTABLE V2 nontargeting siRNA#1 from Dharmacon (Lafayette, CO) was used as a negative control.…”

Section: Sirna Transfectionmentioning

confidence: 99%

“…[7][8][9] The human xb130 gene encodes 818 amino acids and has an apparent molecular size of approximately 130 kDa. As an adaptor protein, the overall structure of XB130 shares similarity with AFAP, so it is also known as actin filament associated protein 1-like 2 (AFAP1L2).…”

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confidence: 99%

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XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

Shiozaki

Lodyga

Bai

et al. 2011

The American Journal of Pathology

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Adaptor proteins with multimodular structures can participate in the regulation of various cellular functions. We have cloned a novel adaptor protein, XB130, which binds the p85␣ subunit of phosphatidyl inositol 3-kinase and subsequently mediates signaling through RET/ PTC in TPC-1 thyroid cancer cells. In the present study, we sought to determine the role of XB130 in the tumorigenesis in vivo and in related molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130 using small interfering RNA inhibited G 1 -S phase progression, induced spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis. Microarray analysis identified 246 genes significantly changed in XB130 shRNA transfected cells. Among them, 57 genes are related to cell proliferation or survival, including many transcription regulators. Ingenuity Pathway Analysis showed that the topranked disease related to XB130 is cancer, and the top molecular and cellular functions are cellular growth and proliferation and cell cycle. A human thyroid tissue microarray study identified expression of XB130 in normal thyroid tissue as well as in human thyroid carcinomas. These observations suggest that the expression of XB130 in these cancer cells may affect cell proliferation and survival by controlling the expression of multiple genes, especially transcription regulators.

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confidence: 67%

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confidence: 81%

“…9 Antibody for GAPDH came from Santa Cruz Biotechnology (Santa Cruz, CA). Anti-PCNA antibody came from Abcam (Cambridge, MA).…”

Section: Cell Lines Antibodies and Other Reagentsmentioning

confidence: 99%

Section: Sirna Transfectionmentioning

confidence: 99%

mentioning

confidence: 99%

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XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

Shiozaki

Lodyga

Bai

et al. 2011

The American Journal of Pathology

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Multivariate Analysis of Several Molecular Markers and Clinicopathological Features in Postoperative Prognosis of Hepatocellular Carcinoma

Zuo

Huang

Shi

et al. 2011

The Anatomical Record

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This study was designed to assess the impact of several molecular markers and clinicopathological characteristics on postoperative survival of patients with hepatocellular carcinoma (HCC). Postoperative clinical data of 64 patients with HCC were retrospectively analyzed. K-ras, PIK3CA, and BRAF gene mutations in surgically resected specimens of the 64 patients with HCC were detected by pyrosequencing. H-ras and XB130 protein expression was examined by immunohistochemistry. A Cox proportional hazards regression model was used for univariate and multivariate survival analyses of the clinical and pathological parameters. The mutation rates of K-ras, PIK3CA, and BRAF genes in HCC were found to be 4.69%, 1.56%, and 0%, respectively. Positive expression rate of XB130 and H-ras in HCC was 75.0% and 93.8%, respectively. Univariate analysis revealed that clinicopathological factors impacting postoperative prognosis of patients with HCC include clinical stage, tumor diameter, and postoperative transcatheter arterial embolization therapy for HCC. Meanwhile, multivariate analysis showed that clinical stage (relative risk [RR]: 6.420, P ¼ 0.013) and tumor diameter (RR: 1.498, P ¼ 0.014) were independent factors impacting postoperative survival of patients with HCC. These findings indicate that the clinical stage and tumor diameter are independent risk factors impacting postoperative survival of patients with HCC. Gene mutations of K-ras and PIK3CA and protein expression of XB130 and H-ras are not associated with the postoperative prognosis of patients with HCC. Anat Rec,

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AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers

et al. 2014

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We have previously identified actin filament-associated protein 1-like 1 (AFAP1L1) as a metastasis-predicting marker for spindle cell sarcomas by gene expression profiling, and demonstrated that AFAP1L1 is involved in the cell invasion process by in vitro analyses. However, its precise molecular function has not been fully elucidated, and it remains unknown whether AFAP1L1 could be a prognostic marker and/or therapeutic target of other malignancies. In this study, we found a marked elevation of AFAP1L1 gene expression in colorectal cancer (CRC) tissues as compared to the adjacent normal mucosa. Multivariate analysis revealed that AFAP1L1 was an independent and significant factor for the recurrence of rectal cancers. Moreover, the addition of the AFAP1L1 expression level to the lymph node metastasis status provided more predictive information regarding postoperative recurrence in rectal cancers. AFAP1L1-transduced CRC cells exhibited a rounded shape, increased cell motility on planar substrates, and resistance to anoikis in vitro. AFAP1L1 localized to the ringed structure of the invadopodia, together with vinculin, and AFAP1L1 was identified as a novel associating partner of vinculin by immunoprecipitation assay. AFAP1L1-transduced cells showed accelerated tumor growth in vivo, presumably reflecting the anoikis resistance of these AFAP1L1-expressing cells. Furthermore, the local administration of a siRNA against AFAP1L1 significantly suppressed the in vivo tumor growth of xenografts, suggesting that AFAP1L1 might be a candidate therapeutic target for CRCs. These results suggest that AFAP1L1 plays a role in the progression of CRCs by modulating cell shape and motility and by inhibiting anoikis, presumably through interactions with vinculin-including protein complexes.

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XB130, a Novel Adaptor Protein for Signal Transduction

Cited by 77 publications

References 54 publications

XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

Multivariate Analysis of Several Molecular Markers and Clinicopathological Features in Postoperative Prognosis of Hepatocellular Carcinoma

AFAP1L1, a novel associating partner with vinculin, modulates cellular morphology and motility, and promotes the progression of colorectal cancers

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