Down-regulation of Lsm1 is involved in human prostate cancer progression

Takahashi, Satoru; Suzuki, Shugo; Inaguma, Shingo; Cho, Young‐Man; Ikeda, Yoshihisa; Hayashi, Norio; Inoue, Takahiro; Sugimura, Yoshiki; Nakatani, Naoki; Fujita, Tamio; Shirai, Tomoyuki

doi:10.1038/sj.bjc.6600163

Cited by 16 publications

(14 citation statements)

References 26 publications

(25 reference statements)

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“…They also reported that CaSm was not expressed in two prostate cancer-derived cell lines, PC3 and DU145 (33). In this study, we find that CaSm protein expression is low in primary normal prostate epithelial cells compared with prostate cancer-derived cell lines.…”

Section: Discussionmentioning

confidence: 51%

CaSm-Mediated Cellular Transformation Is Associated with Altered Gene Expression and Messenger RNA Stability

Fraser¹,

Watson

Fraig³

et al. 2005

Cancer Research

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CaSm (cancer-associated Sm-like) was originally identified based on elevated expression in pancreatic cancer and in several cancer-derived cell lines. CaSm encodes a 133 amino acid protein that contains two Sm motifs found in the common small nuclear RNA proteins and the LSm (like-Sm) family of proteins. Compared with normal human prostate tissue and primary prostate epithelial cells, some primary prostate tumors and prostate cancer-derived cell lines have elevated CaSm expression. Expression of antisense CaSm RNA in DU145 cells results in reduced CaSm protein levels and less transformed phenotype, measured by anchorage-independent growth in vitro and tumor formation in severe combined immunodeficient mice in vivo. Additional data shows that adenoviral delivery of antisense CaSm inhibits the growth of prostate cancer cell lines by altering cell cycle progression, and is associated with reduced expression of cyclin B1 and CDK1 proteins. Consistent with failure of antisense-treated cells to enter mitosis, microarray analysis identified altered expression of NEK2 and nucleophosmin/B23. Although the mechanisms by which CaSm contributes to neoplastic transformation and cellular proliferation are unknown, it has been shown that the yeast homologue (spb8/LSm1) of CaSm is required for 5Vto 3V degradation of specific mRNAs. We provide data consistent with a similar role for CaSm in human cells, supporting the hypothesis that elevated CaSm expression observed in cancer leads to destabilization of multiple gene transcripts, contributing to the mutator phenotype of cancer cells. (Cancer Res 2005; 65(14): 6228-36)

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Section: Discussionmentioning

confidence: 51%

CaSm-Mediated Cellular Transformation Is Associated with Altered Gene Expression and Messenger RNA Stability

Fraser¹,

Watson

Fraig³

et al. 2005

Cancer Research

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“…LSM1 is mapped on chromosome 8p11.2, which has been identified in both prostate cancer [78] and CRC. Although SMN1 has not been identified in cancer directly, it has been proposed to interact with BCL-2, which is associated with CRC, and has a high prognostic value [84,85]. From this analysis, it can be stated that common and unique cliques identified across population networks are involved in important biological processes in CRC.…”

Section: Resultsmentioning

confidence: 99%

Cliques for the identification of gene signatures for colorectal cancer across population

2012

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BackgroundColorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. Studies have correlated risk of CRC development with dietary habits and environmental conditions. Gene signatures for any disease can identify the key biological processes, which is especially useful in studying cancer development. Such processes can be used to evaluate potential drug targets. Though recognition of CRC gene-signatures across populations is crucial to better understanding potential novel treatment options for CRC, it remains a challenging task.ResultsWe developed a topological and biological feature-based network approach for identifying the gene signatures across populations. In this work, we propose a novel approach of using cliques to understand the variability within population. Cliques are more conserved and co-expressed, therefore allowing identification and comparison of cliques across a population which can help researchers study gene variations. Our study was based on four publicly available expression datasets belonging to four different populations across the world. We identified cliques of various sizes (0 to 7) across the four population networks. Cliques of size seven were further analyzed across populations for their commonality and uniqueness. Forty-nine common cliques of size seven were identified. These cliques were further analyzed based on their connectivity profiles. We found associations between the cliques and their connectivity profiles across networks. With these clique connectivity profiles (CCPs), we were able to identify the divergence among the populations, important biological processes (cell cycle, signal transduction, and cell differentiation), and related gene pathways. Therefore the genes identified in these cliques and their connectivity profiles can be defined as the gene-signatures across populations. In this work we demonstrate the power and effectiveness of cliques to study CRC across populations.ConclusionsWe developed a new approach where cliques and their connectivity profiles helped elucidate the variation and similarity in CRC gene profiles across four populations with unique dietary habits.

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“…The first study, using human primary and metastatic prostate samples, concluded that Lsm1/CaSm serves as a metastasis suppressor in prostate cancer samples. 32 The investigators also noted that stable Lsm1 transfection in PC3 cells did not increase proliferation or invasion in vitro . 32 These results are directly at odds with our work and difficult to rationalize given not only the data presented here but also in the context of other investigations supporting that CaSm overexpression promotes a tumorigenic phenotype in many cancer pathologies, including prostate cancer.…”

Section: Discussionmentioning

confidence: 98%

The CaSm (LSm1) oncogene promotes transformation, chemoresistance and metastasis of pancreatic cancer cells

et al. 2016

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The cancer-associated Sm-like (CaSm) oncogene is overexpressed in 87% of human pancreatic tumor samples and CaSm knockdown has demonstrated therapeutic efficacy in murine models of pancreatic cancer. Evidence indicates that CaSm modulates messenger RNA degradation; however, its target genes and the mechanisms by which CaSm promotes pancreatic cancer remain largely unknown. Here, we demonstrate that the CaSm overexpression alters several hallmarks of cancer—including transformation, proliferation, chemoresistance and metastasis. Doxycycline-induced CaSm expression enhanced proliferation and both anchorage-dependent and -independent growth of the human Panc-1 cells in vitro. CaSm induction decreased gemcitabine-induced cytotoxicity and altered the expression of apoptotic regulation genes, including Bad, E2F1 and Bcl-XL. CaSm-overexpressing Panc-1 cells were twofold more migratory and fourfold more invasive than the driver controls and demonstrated characteristics of epithelial-to-mesenchymal transition such as morphological changes and decreased E-cadherin expression. CaSm induction resulted in changes in RNA expression of metastasis-associated genes such as MMP1, SerpinB5, uPAR and Slug. Using a murine model of metastatic pancreatic cancer, injection of CaSm-induced Panc-1 cells resulted in a higher abundance of hepatic metastatic lesions. Overall, CaSm overexpression contributed to a more aggressive cancer phenotype in Panc-1 cells, further supporting the use of CaSm as a therapeutic target against pancreatic cancer.

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Down-regulation of Lsm1 is involved in human prostate cancer progression

Cited by 16 publications

References 26 publications

CaSm-Mediated Cellular Transformation Is Associated with Altered Gene Expression and Messenger RNA Stability

CaSm-Mediated Cellular Transformation Is Associated with Altered Gene Expression and Messenger RNA Stability

Cliques for the identification of gene signatures for colorectal cancer across population

The CaSm (LSm1) oncogene promotes transformation, chemoresistance and metastasis of pancreatic cancer cells

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