Stathmin Activity Influences Sarcoma Cell Shape, Motility, and Metastatic Potential

Belletti, Barbara; Nicoloso, Milena S.; Schiappacassi, Mónica; Berton, Stefania; Lovat, Francesca; Wolf, Katarina; Canzonieri, Vincenzo; D'Andrea, Sara; Zucchetto, Antonella; Friedl, Peter; Colombatti, Alfonso; Baldassarre, Gustavo

doi:10.1091/mbc.e07-09-0894

Cited by 122 publications

(146 citation statements)

References 39 publications

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“…It suggests that some pathogens including inflammatory factors could induce stathmin expression in liver tissue. Furthermore, up-regulated expression of stathmin was also relative to HCC metastasis, consistent with some literature (20)(21)(22)(23). Interestingly, stathmin expression is similar to alpha fetoprotein (AFP), an important biomarker for HCC diagnosis and prognosis.…”

Section: Discussionsupporting

confidence: 87%

Up-regulated expression of stathmin may be associated with hepatocarcinogenesis

Gan

Guo²,

Li³

et al. 2010

Oncol Rep

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Abstract. Stathmin is a microtubule-destabilizing protein ubiquitously expressed in vertebrates and overexpressed in a variety of human malignancies. Down-regulation of its expression will contribute to optimize therapeutic outcomes in the treatment of these malignancies. This research aimed to demonstrate effects of stathmin expression silencing on hepatocellular carcinoma (HCC) cell proliferation, apoptosis, cell adhesion and motility behavior in vitro and further reveal significance of stathmin expression in tissues associated with hepatocarcinogenesis. The expression of stathmin in normal liver, hepatitis, cirrhosis and HCC tissues was detected by immunohistochemistry analysis (IHC), stathmin expression was inhibited in an HCC cell line-HCCLM3 with high metastatic potential by small interfering RNAs (siRNAs). After transfection with siRNAs, HCCLM3 cells proliferation was detected by CCK-8 (cell count kit), cell apoptosis was analyzed by FACS, cell adhesion was investigated by cell adhesion assay and motility ability was demonstrated by in vitro migration and invasion assays. Stathmin expression was up-regulated in HCC tissues, especially in metastatic HCC tissues, compared with normal liver, hepatitis and hepatic cirrhosis tissues. Expression of stathmin in HCCLM3 cells was efficiently inhibited by specific siRNAs. Silencing of stathmin expression obviously suppressed HCCLM3 cell proliferation and markedly induced cell apoptosis. Moreover, defect of stathmin expression in HCCLM3 cell inhibited cell adhesion, restrained cell migration and repressed invasion. Stathmin expression correlates with hepatocarcinogenesis and tumor progression. This molecule may be a promising therapeutic target in patients with hepatocellular carcinoma.

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Section: Discussionsupporting

confidence: 87%

Up-regulated expression of stathmin may be associated with hepatocarcinogenesis

Gan

Guo²,

Li³

et al. 2010

Oncol Rep

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show abstract

“…Elongated cells could be indicative of the more migratory and invasive macrophages during inflammation (73), and cell spreading could create a larger surface area for an encounter with pathogens (25). A recent RNAi screen for cell morphologies identified stathmin as an important regulator of cell shape (74), which confirmed earlier work in a human fibrosarcoma cell line (75). Here, we provide detailed cellular phenotypic and ultrastructural evidence to support a key role for stathmin in cell morphology.…”

Section: Discussionsupporting

confidence: 84%

Down-regulation of Stathmin Is Required for the Phenotypic Changes and Classical Activation of Macrophages

Harrison

2015

Journal of Biological Chemistry

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Background: Macrophage activation involves pronounced microtubule (MT) stabilization. Results: Stathmin is degraded to enhance MT stabilization and allow robust activation in IFN␥-LPS-stimulated macrophages. Conclusion: MT stabilization by reduced stathmin levels is required for enhanced phagocytosis, signal transduction, and activation of macrophages. Significance: Understanding the nature and mechanisms of MT stabilization in activated macrophages is important for both immunology and cell biology fields.

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“…It is overexpressed in trophoblastic tumor and hepatocellular carcinoma, in which it is supposed to play promoting roles in their malignant phenotypes (32,33). STMN-1 encodes stathmin/oncoprotein-18 that is overexpressed in breast cancer, hepatocellular carcinoma, sarcoma, and lung adenocarcinoma (34)(35)(36)(37). Stathmin/oncoprotein-18 has been found to be associated with MAPK and promotes cell-cycle progression (38).…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer

Ikeda

Tanji

Makino

et al. 2012

Molecular Cancer Research

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Aberrant expression of microRNAs (miRNA) is associated with phenotypes of various cancers, including pancreatic cancer. However, the mechanism of the aberrant expression is largely unknown. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in gene expression related to the malignant phenotype of pancreatic cancer. Hence, we studied the role of MAPK in the aberrant expression of miRNAs in pancreatic cancer cells. The alterations in expression of 183 miRNAs induced by activation or inactivation of MAPK were assayed in cultured pancreatic cancer cells and HEK293 cells by means of the quantitative real-time PCR method. We found that four miRNAs, namely, miR-7-3, miR-34a, miR-181d, and miR-193b, were preferentially associated with MAPK activity. Among these miRNAs, miR-7-3 was upregulated by active MAPK, whereas the others were downregulated. Promoter assays indicated that the promoter activities of the host genes of miR-7-3 and miR-34a were both downregulated by alteration in MAPK activity. Exogenous overexpression of the MAPK-associated miRNAs had the effect of inhibition of the proliferation of cultured pancreatic cancer cells; miR-193b was found to exhibit the most remarkable inhibition. A search for target genes of miR-193b led to identification of CCND1, NT5E, PLAU, STARD7, STMN1, and YWHAZ as the targets. Translational suppression of these genes by miR-193b was confirmed by reporter assay. These results indicate that activation of MAPK may play a significant role in aberrant expression of miRNAs and their associated phenotypes in pancreatic cancer. Mol Cancer Res; 10(2); 259-69. Ó2011 AACR.

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Stathmin Activity Influences Sarcoma Cell Shape, Motility, and Metastatic Potential

Cited by 122 publications

References 39 publications

Up-regulated expression of stathmin may be associated with hepatocarcinogenesis

Up-regulated expression of stathmin may be associated with hepatocarcinogenesis

Down-regulation of Stathmin Is Required for the Phenotypic Changes and Classical Activation of Macrophages

MicroRNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer

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