Protein 4.1B suppresses prostate cancer progression and metastasis

Wong, Sunny Y.; Haack, Herbert; Kissil, Joseph L.; Barry, Marc; Bronson, Roderick T.; Shen, Steven S.; Whittaker, Charles A.; Crowley, Denise; Hynes, Richard O.

doi:10.1073/pnas.0705499104

Cited by 65 publications

(68 citation statements)

References 38 publications

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“…Further examination to find such a molecular complex is necessary to determine functional relevance of membrane skeletons including 4.1-family proteins in seminiferous tubules, and also analyses of CADM1-deficient seminiferous tubules may help to understand the membrane skeletal complex. In addition, some 4.1-family proteins have been documented to have a tumor-suppression function (Wong et al 2007). Another question about the 4.1G in the Sertoli and germ cells is whether it plays a role in tumor progression and appearance of phenotypes in testicular tumors without the 4.1G protein.…”

Section: Discussionmentioning

confidence: 99%

Involvement of a membrane skeletal protein, 4.1G, for Sertoli/germ cell interaction

Terada¹,

Ohno²,

Saitoh³

et al. 2010

Reproduction

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We previously reported that a membrane skeletal protein, 4.1G (also known as EPB41L2), is immunolocalized in mouse seminiferous tubules. In this study, the 4.1G immunolocalizaiton was precisely evaluated at various stages of the mouse seminiferous epithelial cycle with 'in vivo cryotechnique' and also with pre-embedding immunoelectron microscopy in testicular tissues whose ultrastructures were well preserved with glycerol treatment before cryosectioning. In addition, 4.1G-deficient mice were produced, and the morphology of their seminiferous tubules was also evaluated. The 4.1G immunolocalization was different among stages, indicating that it was not only along cell membranes of Sertoli cells, but also those of spermatogonia and early spermatocytes. To confirm the 4.1G immunolocalization in germ cells, in vitro culture of spermatogonial stem cells (SSCs) was used for immunocytochemistry and immunoblotting analysis. In the cultured SSCs, 4.1G was clearly expressed and immunolocalized along cell membranes, especially at mutual attaching regions. In testicular tissues, cell adhesion molecule-1 (CADM1), an intramembranous adhesion molecule, was colocalized on basal parts of the seminiferous tubules and immunoprecipitated with 4.1G in the tissue lysate. Interestingly, in the 4.1G-deficient mice, histological manifestation of the seminiferous tubules was not different from that in wild-type mice, and the CADM1 was also immunolocalized in the same pattern as that in the wild-type. Moreover, the 4.1G-deficient male mice were fertile. These results were probably due to functional redundancy of unknown membrane skeletal molecules in germ cells. Thus, a novel membrane skeletal protein, 4.1G, was found in germ cells, and considering its interaction with CADM family, it probably has roles in attachment of both Sertoli-germ and germ-germ cells.

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Section: Discussionmentioning

confidence: 99%

Involvement of a membrane skeletal protein, 4.1G, for Sertoli/germ cell interaction

Terada¹,

Ohno²,

Saitoh³

et al. 2010

Reproduction

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“…Among the approximately 180 targets predicted, 2 genes-EPB41L3 and ALCAM-were previously implicated in suppression of cancer metastasis (20,21). EPB41L3 was of particular interest, because its expression has been found to be progressively lost in gastric cancers, showing increasing degrees of malignancy (22).…”

Section: Mir-223 Posttranscriptionally Downregulates Epb41l3 Expressimentioning

confidence: 99%

miRNA-223 Promotes Gastric Cancer Invasion and Metastasis by Targeting Tumor Suppressor EPB41L3

Zhang²,

Zhang³

et al. 2011

Molecular Cancer Research

322

237

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Traditional research modes aim to find cancer-specific single therapeutic target. Recently, emerging evidence suggested that some micro-RNAs (miRNA) can function as oncogenes or tumor suppressors. miRNAs are singlestranded, small noncoding RNA genes that can regulate hundreds of downstream target genes. In this study, we evaluated the miRNA expression patterns in gastric carcinoma and the specific role of miR-223 in gastric cancer metastasis. miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric carcinomas and confirmed in another 20 paired gastric carcinoma tissues. With the 2-fold expression difference as a cutoff level, we identified 22 differential expressed mature miRNAs. Sixteen miRNAs were upregulated in gastric carcinoma, including miR-223, miR-21, miR-23b, miR-222, miR-25, miR-23a, miR-221, miR-107, miR-103, miR-99a, miR-100, miR-125b, miR-92, miR-146a, miR-214 and miR-191, and six miRNAs were downregulated in gastric carcinoma, including let-7a, miR-126, miR-210, miR-181b, miR-197, and miR-30aa-5p. After examining these miRNAs in several human gastric originated cell lines, we found that miR-223 is overexpressed only in metastatic gastric cancer cells and stimulated nonmetastatic gastric cancer cells migration and invasion. Mechanistically, miR-223, induced by the transcription factor Twist, posttranscriptionally downregulates EPB41L3 expression by directly targeting its 3 0 -untranslated regions. Significantly, overexpression of miR-223 in primary gastric carcinomas is associated with poor metastasis-free survival. These findings indicate a new regulatory mode, namely, specific miRNA, which is activated by its upstream transcription factor, could suppress its direct targets and lead to tumor invasion and metastasis. Mol Cancer Res; 9(7); 824-33. Ó2011 AACR.

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“…Thus, in particular, they evidently exert opposite effects on cell proliferation. Although there is increasing evidence that members of the 4.1 family suppress cell growth and act as tumor suppressors, [43][44][45][46][47] ezrin promotes cell growth and may play a role in tumor metastasis. 48,49 These disparities may be attributable to the different binding partners of these proteins or possibly to different effects of posttranslational modifications on their functions.…”

Section: 1r and T-cell Activation 6135mentioning

confidence: 99%

“…This is consistent with the inference that members of the 4.1 family can function as tumor suppressors. [43][44][45][46][47] Classically, 4.1R and the other family members of this protein have been shown to play important functional roles through their interactions with skeletal proteins such as spectrin and actin. The findings from the present study have identified yet another important role for 4.1R in signal transduction and cell proliferation.…”

Section: 1r and T-cell Activation 6135mentioning

confidence: 99%

Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT

Kang¹,

Yu²,

Pei³

et al. 2009

Blood

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Protein 4.1B suppresses prostate cancer progression and metastasis

Cited by 65 publications

References 38 publications

Involvement of a membrane skeletal protein, 4.1G, for Sertoli/germ cell interaction

Involvement of a membrane skeletal protein, 4.1G, for Sertoli/germ cell interaction

miRNA-223 Promotes Gastric Cancer Invasion and Metastasis by Targeting Tumor Suppressor EPB41L3

Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT

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