SOX7, down-regulated in colorectal cancer, induces apoptosis and inhibits proliferation of colorectal cancer cells

Zhang, Yu; Huang, Shuyan; Dong, Wei; Li, Lin; Feng, Yunpeng; Pan, Lina; Han, Zhenkun; Wang, Xiuli; Ren, Guoling; Su, Dongmei; Huang, Baiqu; Lü, Jun

doi:10.1016/j.canlet.2008.11.014

Cited by 65 publications

(71 citation statements)

References 31 publications

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“…In addition, the observed high levels of Sox7 expression in early secretory stage were also surprising, allowing us to speculate that the gene may be important for changes in cell kinetics from proliferative to secretory stages in normal endometrium, as ectopic expression of Sox7 in Sox-null cells has been demonstrated to inhibit cell proliferation. 30 Together, our observations suggest a model for functional roles of Sox4 in b-catenin/TCF4 signaling in Em Ca cells (Figure 9), dependent on upregulation of the TCF4 gene. Newly synthesized TCF4 binds to excess b-catenin, probably present due to gene mutations, 17,19 and this in turn leads to transactivation of target genes, such as TCF4 and p14 ARF , (ref.…”

Section: Hypermethylation Of Sox7 Promoter In Em Cassupporting

confidence: 56%

“…As hypermethylation of the Sox7 promoter has been reported to frequently occur in tumors, 29,30 we also examined the methylation status in Em Cas for comparison with expression levels. Methylation-specific PCR assays revealed specific signals in seven of eight Em Ca cell lines, with apparent decreases in the mRNA expression levels (Figure 8a).…”

Section: Hypermethylation Of Sox7 Promoter In Em Casmentioning

confidence: 99%

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Sox4 functions as a positive regulator of β-catenin signaling through upregulation of TCF4 during morular differentiation of endometrial carcinomas

Saegusa

Hashimura

Kuwata

2012

Laboratory Investigation

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Sox factors function as either activators or repressors of b-catenin/TCF transcription depending on the cellular context and associated interacting proteins. Our previous study provided evidence that alteration in b-catenin signaling is an essential event during transdifferentiation toward the morular phenotype of endometrial carcinomas (Em Cas). Here, we focused on related functional roles of Sox factors. Of eight Sox factors investigated, Sox4 could enhance b-catenin/TCF4 transcription, through upregulation of TCF4 at the transcription level, without any direct b-catenin association. Cells stably overexpressing Sox4 showed significant decreases in proliferation rate, along with increases in expression of p21 WAF1 , as well as TCF4, in contrast to increased cell growth observed with knockdown. Of these factors, only Sox7 could transcriptionally upregulate Sox4 expression, but it also resulted in not only inhibition of Sox4-meditated activation of b-catenin/TCF4-driven transcription, but also repression of its own promoter activity, indicating the existence of very complex feedback loop for Sox-mediated signal cascades. Finally, Sox4 immunoreactivity was frequently pronounced in morular lesions of Em Cas, the expression being positively correlated with status of b-catenin, TCF4, and Sox7, and inversely with cell proliferation. These data therefore suggest that Sox4 may serve as a positive regulator of b-catenin signaling through alteration in TCF4 expression during morular differentiation of Em Ca cells, leading to inhibition of cell proliferation. In addition, Sox7 may also participate in the process, having complex roles in modulation of signaling.

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Section: Hypermethylation Of Sox7 Promoter In Em Cassupporting

confidence: 56%

Section: Hypermethylation Of Sox7 Promoter In Em Casmentioning

confidence: 99%

Sox4 functions as a positive regulator of β-catenin signaling through upregulation of TCF4 during morular differentiation of endometrial carcinomas

Saegusa

Hashimura

Kuwata

2012

Laboratory Investigation

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“…Many genes playing important roles in apoptosis were down-regulated during tumor progress (11)(12)(13). In this study, we show for the first time that NAIF1 is down-regulated or the expression was lost in gastric cancer tissue.…”

Section: Discussionmentioning

confidence: 63%

NAIF1 is down-regulated in gastric cancer and promotes apoptosis through the caspase-9 pathway in human MKN45 cells

Luo

Zhao²,

Zhong³

et al. 2011

Oncol Rep

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Abstract. Many key proteins are down-regulated or lose their function during cancer genesis and accelerate the progress of cancer. We found that nuclear apoptosis-inducing factor 1 (nAIF1) was highly expressed in normal gastric tissues but was down-regulated or lost in gastric cancer tissues (p<0.001). nAIF1 expression was higher in well-differentiated (p=0.004) than in moderately-or poorly-differentiated gastric cancer. nAIF1 expression was associated with different t stages (p=0.024). In vitro, nAIF1 can inhibit tumor cell proliferation and induce g0/g1 phase cell cycle arrest in the MKn45 cell line. nAIF1 can induce apoptosis through activation of procaspase-9 rather than procaspase-8 followed by activation of the caspase-3 pathway. We designed and constructed two truncation mutants, pegFpn1-nls and pegFp-n1-grr, and identified the n-terminal 1-90 amino acid domain of nAIF1, which is a helix-turn-helix motif and which was sufficient for inducing apoptosis. Therefore, these findings suggest that NAIF1 plays an inhibitory role in the initial steps of gastric cancer genesis and may provide new strategies for developing anti-cancer drugs using small molecular polypeptides. Introductiongastric cancer is a highly frequent malignancy worldwide with an estimated incidence of 934000 new cases per year in 2002 (1,2). More than 42% of gc patients are found in china alone (3). currently, targeted therapies designed to induce apoptosis in cancer cells selectively are the most promising anti-cancer strategies. Many efforts have been made to cure gastric cancer, most of which based on developing effective apoptotic therapeutic approaches such as activation of cell surface death receptors, inhibition of cell survival signaling and others (4-6).nAIF1 (nuclear apoptosis-inducing factor 1) was found to induce apoptosis when overexpressed in Hela and HeK293 cells (7). Another study showed nAIF1 was related to transposition because of its trihelix motif (8). However, little information exists on the relationship between nAIF1 and cancer genesis and progress, thus this study investigated the expression and function of nAIF1 in cancer.We found nAIF1 was highly expressed in normal stomach tissue, but was down-regulated or lost in gastric cancer tissue (P<0.001). This event significantly correlated with the tumor differential t stage. Functional studies indicated nAIF1 can reduce cell viability in human gastric cell line MKn45 by g0/g1 phase cell cycle arrest and induce apoptosis 48 h posttransfection. Western blot analysis indicated nAIF1 triggered procaspase-3 and procaspase-9 activation and pArp cleavage in MKN45. Furthermore, we identified that the 1-90 amino acids domain was the core functional domain of nAIF1 for inducing apoptosis. Thus, our findings provide a potential target for gc apoptotic therapeutic approach. Materials and methodsReagents. Mtt, pI and DApI were purchased from sigma (UsA). Monoclonal antibody against β-actin was purchased from sigma-Aldrich (UsA). the antibody against pArp and procaspase-8 were purchased ...

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“…It encodes a transcription factor that can both enhance and inhibit transcription. SOX7 is mainly implicated in parietal endoderm differentiation [19]. According to the previous studies, SOX7 mRNA is undetected in some human cancer cell lines including HeLa S3 (cervical cancer), K562 (chronic myelogenous leukemia), SW480 (colorectal cancer), etc., suggesting that SOX7 might be a tumor suppressor gene in these cancers [20].…”

Section: Discussionmentioning

confidence: 99%

SOXs in human prostate cancer: implication as progression and prognosis factors

et al. 2012

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BackgroundSOX genes play an important role in a number of developmental processes. Potential roles of SOXs have been demonstrated in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and types. The aim of this study was to investigate the involvement of SOXs in the progression and prognosis of human prostate cancer (PCa).MethodsThe gene expression changes of SOXs in human PCa tissues compared with non-cancerous prostate tissues was detected using gene expression microarray, and confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohositochemistry. The roles of these genes in castration resistance were investigated in LNCaP xenograft model of PCa.ResultsThe microarray analysis identified three genes (SOX7, SOX9 and SOX10) of SOX family that were significantly dis-regulated in common among four PCa specimens. Consistent with the results of the microarray, differential mRNA and protein levels of three selected genes were found in PCa tissues by QRT-PCR analysis and immunohistochemistry. Additionally, we found that the immunohistochemical staining scores of SOX7 in PCa tissues with higher serum PSA level (P = 0.02) and metastasis (P = 0.03) were significantly lower than those with lower serum PSA level and without metastasis; the increased SOX9 protein expression was frequently found in PCa tissues with higher Gleason score (P = 0.02) and higher clinical stage (P < 0.0001); the down-regulation of SOX10 tend to be found in PCa tissues with higher serum PSA levels (P = 0.03) and advanced pathological stage (P = 0.01). Moreover, both univariate and multivariate analyses showed that the down-regulation of SOX7 and the up-regulation of SOX9 were independent predictors of shorter biochemical recurrence-free survival. Furthermore, we discovered that SOX7 was significantly down-regulated and SOX9 was significantly up-regulated during the progression to castration resistance.ConclusionsOur data offer the convince evidence that the dis-regulation of SOX7, SOX9 and SOX10 may be associated with the aggressive progression of PCa. SOX7 and SOX9 may be potential markers for prognosis in PCa patients. Interestingly, the down-regulation of SOX7 and the up-regulation of SOX9 may be important mechanisms for castration-resistant progression of PCa.

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SOX7, down-regulated in colorectal cancer, induces apoptosis and inhibits proliferation of colorectal cancer cells

Cited by 65 publications

References 31 publications

Sox4 functions as a positive regulator of β-catenin signaling through upregulation of TCF4 during morular differentiation of endometrial carcinomas

Sox4 functions as a positive regulator of β-catenin signaling through upregulation of TCF4 during morular differentiation of endometrial carcinomas

NAIF1 is down-regulated in gastric cancer and promotes apoptosis through the caspase-9 pathway in human MKN45 cells

SOXs in human prostate cancer: implication as progression and prognosis factors

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