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Review
. 2021 Aug 29;10(9):2238.
doi: 10.3390/cells10092238.

Schlafens: Emerging Proteins in Cancer Cell Biology

Sarmad Al-Marsoummi  1 , Emilie E Vomhof-DeKrey  1   2 , Marc D Basson  1   2   3
Affiliations
Review

Schlafens: Emerging Proteins in Cancer Cell Biology

Sarmad Al-Marsoummi et al. Cells. .

Abstract

Schlafens (SLFN) are a family of genes widely expressed in mammals, including humans and rodents. These intriguing proteins play different roles in regulating cell proliferation, cell differentiation, immune cell growth and maturation, and inhibiting viral replication. The emerging evidence is implicating Schlafens in cancer biology and chemosensitivity. Although Schlafens share common domains and a high degree of homology, different Schlafens act differently. In particular, they show specific and occasionally opposing effects in some cancer types. This review will briefly summarize the history, structure, and non-malignant biological functions of Schlafens. The roles of human and mouse Schlafens in different cancer types will then be outlined. Finally, we will discuss the implication of Schlafens in the anti-tumor effect of interferons and the use of Schlafens as predictors of chemosensitivity.

Keywords: Schlafen; cancer; differentiation; immune response; invasion; proliferation; signaling.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Diagrammatic representation of Schlafens family in mice and humans. Schlafens are classified into three families: short (grey), intermediate (orange), and long (green). Humans do not express short family Schlafens. All Schlafens share the SLFN box and putative AAA domains, while the SWADL domain is found in only intermediate and long Schlafens. Long Schlafens have an extra C-terminal helicase domain that harbors a nuclear targeting sequence.
Figure 2
Figure 2
Diagram illustrates the identified effects of different Schlafens on cancer cell biology. The reduced cell proliferation, differentiation, invasion, and stem cells, in addition to the increased differentiation, immune sensitization, and chemosensitivity, all contribute to improved survival.
Figure 3
Figure 3
Analysis of TCGA datasets shows the expression levels of human SLFN5, SLFN11, SLFN12, SLFN13, and SLFN14 in various human tumors. Schlafens were abnormally expressed in pan cancers (right bars) by Tumor, Normal and Metastatic (TNM) plot compared to adjacent normal tissue (left bars). Significant differences by Mann–Whitney U test are labeled with red color and asterisk. Abbreviations: Lung_AC: lung adenocarcinoma; Lung_SC: lung squamous cell carcinoma; Renal_CC: renal clear cell carcinoma; Renal_CH: renal chromophobe cell carcinoma; Renal_PA: renal papillary cell carcinoma; Uterus_CS: uterine carcinosarcoma; Uterus_EC: uterine corpus endometrial carcinoma [75].
See this image and copyright information in PMC

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