STMN2 is a novel target of β-catenin/TCF-mediated transcription in human hepatoma cells

Lee, Heun Sik; Lee, Dong Chul; Park, Mee Hee; Yang, Suk Jin; Lee, Jung Ju; Kim, Dong-Min; Jang, Yejin; Lee, Jae Hyuck; Choi, Jong Young; Kang, Yun Kyung; Kim, Dae Il; Park, Kyung Chan; Kim, Seon‐Young; Yoo, Hyang Sook; Choi, Eui Ju; Yeom, Young Il

doi:10.1016/j.bbrc.2006.05.017

Cited by 24 publications

(16 citation statements)

References 31 publications

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“…To this effect, SW480 cells were used in view of their high transfection capacity, and Tcf-4 activity was stimulated or inhibited by expressing a nondegradable h-catenin mutant (DN87-h-catenin, ref. 28) or the soluble COOH-terminal domain of E-cadherin (27), respectively. Overexpression of the DN87-h-catenin mutant was capable of further stimulating Tcf-4 activity in SW480 cells, as confirmed by TOP/FOP Tcf-4 reporter assay ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells

et al. 2008

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Tight junctions have recently emerged as essential signaling regulators of proliferation and differentiation in epithelial tissues. Here, we aimed to identify the factors regulating claudin-7 expression in the colon, and analyzed the consequences of claudin-7 overexpression in colorectal carcinoma (CRC). In healthy human colonic crypts, claudin-7 expression was found to be low in the stem/progenitor cell compartment, where Tcf-4 activity is high, but strong in differentiated and postmitotic cells, where Tcf-4 is inactive. In contrast, claudin-7 was overexpressed in areas with high Tcf-4 target gene levels in CRC samples. In vitro, Tcf-4 was able to repress claudin-7 expression, and the high mobility group-box transcription factor Sox-9 was identified as an essential mediator of this effect. Claudin-7 was strongly expressed in the intestine of Sox-9-deficient mice and in CRC cells with low Sox transcriptional activity. Sox-9 overexpression in these cells reinstated claudin-7 repression, and residual claudin-7 was no longer localized along the basolateral membrane, but was instead restricted to tight junctions. Using HT-29Cl.16E CRC cell spheroids, we found that Sox-9-induced polarization was completely reversed after virus-mediated claudin-7 overexpression. Claudin-7 overexpression in this context increased Tcf-4 target gene expression, proliferation, and tumorigenicity after injection in nude mice. Our results indicate that Tcf-4 maintains low levels of claudin-7 at the bottom of colonic crypts, acting via Sox-9. This negative regulation seems to be defective in CRC, possibly due to decreased Sox-9 activity, and the resulting claudin-7 overexpression promotes a loss of tumor cell polarization and contributes to tumorigenesis.

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Section: Resultsmentioning

confidence: 99%

Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells

et al. 2008

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“…Of these genes, stathmin-like 2 (Stmn2) was demonstrated to be a direct target of β-catenin/TCF-mediated transcription in hepatoma cells [28]. β-catenin/TCF is frequently activated during embryogenesis [29], consistent with its elevated expression in ES cell culture observed in the signature pattern.…”

Section: Discussionmentioning

confidence: 99%

Using biomarker signature patterns for an mRNA molecular diagnostic of mouse embryonic stem cell differentiation state

et al. 2007

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Background: The pluripotency and self-renewal capabilities, which define the "stemness" state, of mouse embryonic stem (ES) cells, are usually investigated by functional assays or quantitative measurements of the expression levels of known ES cell markers. Strong correlations between these expression levels and functional assays, particularly at the early stage of cell differentiation, have usually not been observed. An effective molecular diagnostic to properly identify the differentiation state of mouse ES cells, prior to further experimentation, is needed.

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“…In contrast to stathmin and SCLIP, the other family members are exclusively expressed in the nervous system under physiologic conditions (5,6). Stathmin, SCG10, SCLIP, and RB3 share a so-called stathmin-like domain that contains up to four phosphorylation sites (stathmin: Ser 16 , Ser 25 , Ser 38 , and Ser…”

Section: Introductionmentioning

confidence: 99%

“…Elevated expression of stathmin supports microtubule-dependent processes and contributes to tumor cell chemoresistance (12,14,15). In addition, one recent report implicated that SCG10 is required for maintaining the anchorage-independent growth state of h-catenin/ TCF-activated hepatoma cells (16). Although many studies clearly defined the microtubule-destabilizing activity of stathmin in different cell lines, the efficient knockdown of stathmin by genespecific short interfering RNA (siRNA) only partially influenced microtubule polymerization in malignant cells suggesting functional compensation by other microtubule catastrophe-promoting factors (12,17).…”

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confidence: 99%

Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

et al. 2009

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Dynamic instability of the microtubule network modulates processes such as cell division and motility, as well as cellular morphology. Overexpression of the microtubule-destabilizing phosphoprotein stathmin is frequent in human malignancies and represents a promising therapeutic target. Although stathmin inhibition gives rise to antineoplastic effects, additional and functionally redundant microtubule-interacting proteins may attenuate the efficiency of this therapeutic approach. We have systematically analyzed the expression and potential protumorigenic effects of stathmin family members in human non-small cell lung cancer (NSCLC). Both stathmin and stathmin-like 3 (SCLIP) were overexpressed in adenocarcinoma as well as squamous cell carcinoma (SCC) tissues and induced tumor cell proliferation, migration, and matrix invasion in respective cell lines. Accordingly, reduced stathmin and SCLIP levels affected cell morphology and were associated with a less malignant phenotype. Combined inhibition of both factors caused additive effects on tumor cell motility, indicating partial functional redundancy. Because stathmin and SCLIP expression significantly correlated in NSCLC tissues, we searched for common upstream regulators and identified the far upstream sequence element-binding protein-1 (FBP-1) as a pivotal inducer of several stathmin family members. Our results indicate that the coordinated overexpression of microtubule-destabilizing factors by FBP-1 is a critical step to facilitate microtubule dynamics and subsequently increases proliferation and motility of tumor cells.

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STMN2 is a novel target of β-catenin/TCF-mediated transcription in human hepatoma cells

Cited by 24 publications

References 31 publications

Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells

Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells

Using biomarker signature patterns for an mRNA molecular diagnostic of mouse embryonic stem cell differentiation state

Coordinated Expression of Stathmin Family Members by Far Upstream Sequence Element-Binding Protein-1 Increases Motility in Non–Small Cell Lung Cancer

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