Preliminary Research on the Expression, Purification and Function of the Apoptotic Fusion Protein, Sival

Zhang, Yahan; Yu, Lu‐Gang; Zhu, Wan-Zhan; Wang, Shengli; Wang, Dian-Dong; Yang, Yan-Xin; Xia, Yu

doi:10.7314/apjcp.2014.15.20.8685

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…Taken together, stable knockdown of SIVA in 231L cells significantly enhanced cell migration and invasion, effects that were reversed after re-introducing the expression of SIVA-WT. This highly suggests that SIVA is involved in the regulation of 231L cell mobility and invasiveness as previously reported in other cell lines such as breast MCF7 and colorectal HCT116 cells [21,42], and now validated in MB-MDA-231 cells.…”

Section: Plos Onesupporting

confidence: 82%

Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo

Vermehren-Schmaedick,

Peto,

Wagoner

et al. 2024

PLoS ONE

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Metastasis is the most dreaded outcome after a breast cancer diagnosis, and little is known regarding what triggers or promotes breast cancer to spread distally, or how to prevent or eradicate metastasis effectively. Bilateral breast cancers are an uncommon form of breast cancers. In our study, a percentage of bilateral breast cancers were clonally related based on copy number variation profiling. Whole exome sequencing and comparative sequence analysis revealed that a limited number of somatic mutations were acquired in this “breast-to-breast” metastasis that might promote breast cancer distant spread. One somatic mutation acquired was SIVA-D160N that displayed pro-metastatic phenotypes in vivo and in vitro. Over-expression of SIVA-D160N promoted migration and invasion of human MB-MDA-231 breast cancer cells in vitro, consistent with a dominant negative interfering function. When introduced via tail vein injection, 231 cells over-expressing SIVA-D160N displayed enhanced distant spread on IVIS imaging. Over-expression of SIVA-D160N promoted invasion and anchorage independent growth of mouse 4T1 breast cancer cells in vitro. When introduced orthotopically via mammary fat pad injection in syngeneic Balb/c mice, over-expression of SIVA-D160N in 4T1 cells increased orthotopically implanted mammary gland tumor growth as well as liver metastasis. Clonally related bilateral breast cancers represented a novel system to investigate metastasis and revealed a role of SIVA-D160N in breast cancer metastasis. Further characterization and understanding of SIVA function, and that of its interacting proteins, may elucidate mechanisms of breast cancer metastasis, providing clinically useful biomarkers and therapeutic targets.

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Section: Plos Onesupporting

confidence: 82%

Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo

Vermehren-Schmaedick,

Peto,

Wagoner

et al. 2024

PLoS ONE

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“…Previous research found that bacterially expressed Siva 1 performed anticancer activities: suppressed the invasion, migration and induced apoptosis of colon cancer cells. 11 In addition, Siva 1 protein also found significantly inhibited the tumor metastasis of the nasopharyngeal carcinoma tumor-bearing mice. 22 Based on the former study, we hypothesized that Siva 1 may play a role in the migration and invasion of cervical cancer.…”

Section: Discussionmentioning

confidence: 92%

“…10 Whatsmore, His-Siva 1 recombinant protein was found to inhibit migration and invasion of HCT116 cells. 11 And our previous study found that Siva 1 plays a role in restricting EMT and inducing apoptosis by phosphorylation of stathmin and polymerization of α-tubulin. 12 Despite these studies, the expression of Siva 1 in cervical cancer and its biological function are still unclear.…”

Section: Introductionmentioning

confidence: 93%

<p>Siva 1 Inhibits Cervical Cancer Progression and Its Clinical Prognosis Significance</p>

Liu¹,

Ma²,

Wang³

et al. 2020

CMAR

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Background: Cervical cancer is the second most common female malignancies. But the exact etiology of cervical cancer is still under investigation. Recent observations revealed that the loss expression of Siva 1 was related to several different types of tumors. It could play an indispensable role in both exogenous and endogenous apoptotic signaling pathways. Nevertheless, the relationship between Siva 1 expression and cervical cancer progression has not yet been fully clarified. This study aimed to explore the functional role of Siva1 in cervical cancer. Materials and Methods: In this present experiment, expression of Siva 1 was detected in 87 cervical cancer, 34 CIN and 20 normal samples by immunohistochemistry. The correlation of Siva 1 expression and overall survival times (OS) was analyzed by Kaplan-Meier analysis. We up-regulated the expression of Siva 1 by plasmid pCMV3-Siva 1 in C33A cells. CCK8, flow cytometry, wound-healing, and transwell assays were performed to examine the influences of Siva 1 expression on cell proliferation, apoptosis, migration and invasion. Results: The expression of Siva 1 was decreased in cervical cancer tissues compared with CIN and normal tissues. In addition, the Siva 1 immunoreactivity was significantly associated with tumor differentiation. Patients with Siva 1 negative staining exhibited a significantly decreased overall survival. Then, we established stable Siva 1 ectopic expression cells, and we found that elevated expression of Siva 1 promoted apoptosis, inhibited proliferation, and suppressed migration and invasion of cervical cancer cells. Conclusion: The present study revealed a crucial role of Siva 1 in tumor progression and it may be a valuable prognostic indicator of cervical cancer.

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“…His-Siva-1 recombinant protein inhibited invasion and migration of HCT116 cells. 19 The C-terminal domain (aa residues 84-175) expressed in bacteria as a GST-fusion protein caused apoptosis in Jurkat leukemia cells and its biophysical properties were studied. 20 The authors found monodispersion of the protein in solution with a predominant unfolded and elongated shape.…”

Section: Siva-1 Is a Proapoptotic Protein With Anticancer Activitymentioning

confidence: 99%

Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene

Vachtenheim

Lischke

2018

OTT

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Siva-1 is a typical apoptotic protein commonly activated by the p53 tumor suppressor protein and should therefore participate in a barrier against the development of cancer. It has proapoptotic activities in various cell systems. Recent findings suggest that Siva-1 possesses several other apoptosis-independent functions and interacts with many other proteins not directly involved in apoptosis. It harbors the ARF E3 ubiquitin protein ligase activity, a property that is clearly prooncogenic and leads to p53 degradation through the upregulation of the Hdm2 protein level. Surprisingly, recent evidence shows that Siva-1 absence prevents the development of non-small cell lung carcinomas in a mouse model and reveals the oncogenic roles in the same types of human cells, indicating its unique function as an oncogene in the cell context-dependent manner. Herein, we review reported activities of Siva-1 in various experimental settings and comment on its ambiguous function in tumor biology.

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Preliminary Research on the Expression, Purification and Function of the Apoptotic Fusion Protein, Sival

Abstract: The objective of the present study was to investigate cloning, expression, and functions of the recombinant protein, Siva1.

Cited by 4 publications

References 12 publications

Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo

Mutation of SIVA, a candidate metastasis gene identified from clonally related bilateral breast cancers, promotes breast cancer cell spread in vitro and in vivo

<p>Siva 1 Inhibits Cervical Cancer Progression and Its Clinical Prognosis Significance</p>

Siva-1 emerges as a tissue-specific oncogene beyond its classic role of a proapoptotic gene

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