Schlafen 12 expression modulates prostate cancer cell differentiation

Kovalenko, Pavlo L.; Basson, Marc D.

doi:10.1016/j.jss.2014.03.069

Cited by 24 publications

(29 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SLFN12 has previously been reported to alter the phenotype of other cells, including prostatic cancer cells [53] and activated T cells [54, 55], and to inhibit dendritic cell differentiation [11]. Slfn4, also intermediate length, regulates myelopoiesis [56].…”

Section: Discussionmentioning

confidence: 99%

Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation

Basson

Wang

Chaturvedi

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Human enterocytic differentiation is altered during development, fasting, adaptation, and bariatric surgery, but its intracellular control remains unclear. We hypothesized that Schlafen 12 (SLFN12) regulates enterocyte differentiation. Methods: We used laser capture dissection of epithelium, qRT-PCR, and immunohistochemistry to evaluate SLFN12 expression in biopsies of control and fasting human duodenal mucosa, and viral overexpression and siRNA to trace the SLFN12 pathway in human Caco-2 and HIEC6 intestinal epithelial cells. Results: Fasting human duodenal mucosa expressed less SLFN12 mRNA and protein, accompanied by decreases in enterocytic markers like sucrase-isomaltase. SLFN12 overexpression increased Caco-2 sucrase-isomaltase promoter activity, mRNA, and protein independently of proliferation, and activated the SLFN12 putative promoter. SLFN12 coprecipitated Serpin B12 (SERPB12). An inactivating SLFN12 point mutation prevented both SERPB12 binding and sucrase-isomaltase induction. SERPB12 overexpression also induced sucrase-isomaltase, while reducing SERPB12 prevented the SLFN12 effect on sucrase-isomaltase. Sucrase-isomaltase induction by both SLFN12 and SERPB12 was attenuated by reducing UCHL5 or USP14, and blocked by reducing both. SERPB12 stimulated USP14 but not UCHL5 activity. SERPB12 coprecipitated USP14 but not UCHL5. Moreover, SLFN12 increased protein levels of the sucrase-isomaltase-promoter-binding transcription factor cdx2 without altering Cdx2 mRNA. This was prevented by reducing UCHL5 and USP14. We further validated this pathway in vitro and in vivo. SLFN12 or SERPB12 overexpression induced sucrase-isomaltase in human non-malignant HIEC-6 enterocytes. Conclusions: SLFN12 regulates human enterocytic differentiation by a pathway involving SERPB12, the deubiquitylases, and Cdx2. This pathway may be targeted to manipulate human enterocytic differentiation in mucosal atrophy, short gut or obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation

Basson

Wang

Chaturvedi

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Human SLFN11 has been shown to inhibit viral protein synthesis in HIV-infected cells (32) and to sensitize malignant cells to DNA-damaging agents and other chemotherapeutic cells (15). Human SLFN5 has been implicated in the control of anchorage-independent growth of malignant melanoma cells (18), while human SLFN12 has been im- plicated in the control of differentiation of prostate epithelial cells (13).…”

Section: Discussionmentioning

confidence: 99%

“…There are several human and mouse genes that are members of the SLFN family (9,11). Prior evidence has implicated members of the Schlafen family in the regulation of tumorigenesis (13)(14)(15)(16)(17)(18). Notably, expression of various members of this family is upregulated following treatment with type I IFNs (17)(18)(19), cytokines known to promote induction of antineoplastic, antiviral, and immunoregulatory effects (1)(2)(3)(4).…”

mentioning

confidence: 99%

Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells

Sassano

Mavrommatis

Arslan

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

We provide evidence that human SLFN5, an interferon (IFN)-inducible member of the Schlafen (SLFN) family of proteins, exhibits key roles in controlling motility and invasiveness of renal cell carcinoma (RCC) cells. Our studies define the mechanism by which this occurs, demonstrating that SLFN5 negatively controls expression of the matrix metalloproteinase 1 gene (MMP-1), MMP-13, and several other genes involved in the control of malignant cell motility. Importantly, our data establish that SLFN5 expression correlates with a better overall survival in a large cohort of patients with RCC. The inverse relationship between SLFN5 expression and RCC aggressiveness raises the possibility of developing unique therapeutic approaches in the treatment of RCC, by modulating SLFN5 expression. Interferons (IFNs) are cytokines with important antineoplastic activities and therefore are frequently utilized in the treatment of cancer (1-4). A malignancy that exhibits sensitivity to interferon treatment is renal cell carcinoma (RCC) (5). RCC is the most common type of kidney tumor in humans and is associated with high morbidity and mortality (6, 7). In general, patients with recurrent or advanced disease have limited treatment options and a very poor overall prognosis (7). The Schlafen (SLFN) family of genes includes several members that share structural homology and play regulatory roles in the control of cell cycle progression and cell growth arrest (8-12). There are several human and mouse genes that are members of the SLFN family (9, 11). Prior evidence has implicated members of the Schlafen family in the regulation of tumorigenesis (13)(14)(15)(16)(17)(18). Notably, expression of various members of this family is upregulated following treatment with type I IFNs (17-19), cytokines known to promote induction of antineoplastic, antiviral, and immunoregulatory effects (1-4). Despite the induction of human and mouse SLFN genes by IFNs, the precise mechanisms by which SLFNs mediate antineoplastic responses in different types of malignant human cells remain to be determined.In the present study, we provide evidence that the expression of human SLFN5 is inducible by type I IFN receptor. SLFN5, like other long SLFNs, is characterized by a large C-terminal extension, a DNA/RNA helicase domain, and a nuclear localization sequence (NLS) (9, 20). Although SLFN5 is induced in melanoma cells following IFN treatment (18), the role of SLFN5 in tumor progression is largely unknown.In efforts to define the functional implications of SLFN5 expression in malignant RCC cells, we found that SLFN5 repressed the motility and invasiveness of malignant renal cell carcinoma cells, by negatively controlling the expression of matrix metalloproteinase (MMP) genes, such as MMP-1 and MMP-13. Importantly, analysis of SLFN5 mRNA expression in a large number of samples from a cohort of RCC patients demonstrated that SLFN5 expression correlates with better overall survival of RCC patients. Altogether, our studies for the first time establish a mechanism by which...

show abstract

“…In contrast, the level of slfn4 is high in primitive bone marrow cells, but low in macrophages (van Zuylen et al, 2011). (4) Slfn members inhibit migration and invasion of cancer cells and sensitize cancers to chemotherapy (Kovalenko and Basson, 2014;Tian et al, 2014). In addition, recent studies have shown that slfn protein can serve as markers of gastric metaplasia (Ding et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…However, the specific location and relative functions of human slfns are not well understood. H-slfn5 was identified to localize in the nucleus (Katsoulidis et al, 2010), while h-slfn12 and h-slfn11 were indicated to localize in the cytosol (Li et al, 2012;Kovalenko and Basson, 2014).…”

Section: Introductionmentioning

confidence: 99%

The Schlafen family: complex roles in different cell types and virus replication

Liu

Zhou

Wang

et al. 2017

Cell Biology International

View full text Add to dashboard Cite

The Schlafen (slfn) gene family members express broadly, but the research has mainly focused on human slfn (h-slfn) and mouse slfn (m-slfn). The slfn members can be divided into three groups, and each group has its own characteristics and functions. Although the effects of slfns are still poorly understood, it has been confirmed that slfns are involved in the defense of immune system and regulate immune cells' proliferation and differentiation. In some malignant tumors, the slfn proteins can inhibit the growth and invasion of cancer cells, promote cancer cells sensibility to chemotherapeutics, and can be a promising new therapeutic target. In addition, the slfn proteins also disturb replication and virulence of viruses. In this review, we summarize the characteristics of the Schlafen family's structures and functions with the aim to achieve a more comprehensive understanding of slfns.

show abstract

Schlafen 12 expression modulates prostate cancer cell differentiation

Cited by 24 publications

References 43 publications

Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation

Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation

Human Schlafen 5 (SLFN5) Is a Regulator of Motility and Invasiveness of Renal Cell Carcinoma Cells

The Schlafen family: complex roles in different cell types and virus replication

Contact Info

Product

Resources

About