Cystatin E/M Proteins (CST6)

Human Cystatin E/M (CST6) interaction partners

1. High CST6 expression is associated with lymph-node metastasis in Triple-Negative Breast Cancer.

2. Data suggest that melanoma cells internalize/absorb cystatin C from culture media, leading to increased intracellular cystatin C levels; cystatin E/M is internalized as well but at modest rate due to down-regulation of cell migration; however, the effect of intracellular cystatin E/M on down-regulation of legumain activity is pronounced.

3. Results provide evidence that cystatin E/M is a tumor suppressor gene which plays an important role in the regulation of NF-kappaB.

4. Low CST6 expression is associated with breast cancer.

5. Developed a Methylation-Sensitive High Resolution Melting Analysis (MS-HRMA) assay for the investigation of CST6 promoter methylation in breast cancer patients.CST6 promoter was methylated in 39/80 of FFPEs.

6. The CST6 promoter is highly methylated in circulating cell-free DNA of breast cancer patients, but not in healthy individuals.

7. Data show a regulatory role of cystatin E/M in controlling both intra- and extracellular legumain activity.

8. The ectopic expression of CST6 in cancer cells rescued mice from overt osteolytic metastasis and deaths in the animal study, while CST6 knockdown markedly enhanced cancer cell bone metastasis and shortened animal survival.

9. An association between the quantity of CST6 methylation and the expression statuses of estrogen receptor, progesterone receptor, and HER4 in tumor tissues was found

10. the level of cystatin E/M regulates legumain activity and hence the invasive potential of human melanoma cells

11. CST6 is not a major gene contributing to type 1 and 2 harlequin ichthyosis

12. Cystatin M suppresses the malignant phenotype of MDA-MB-435S cells.

13. Complete loss of expression of cystatin M was observed in two of three stage IV breast cancer patients. Immunohistochemical studies confirmed that expression of cystatin M in IDCs was partially or completely lost.

14. This study thus provides the first evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression.

15. Identification of CTSV & CTSL as targets for cystatin M/E, their (co)-expression in the stratum granulosum of skin, and activity of CTSL toward transglutaminase 3 strongly imply an important role for them in the differentiation process of human epidermis.

16. Tumors displaying CST6 gene methylation, display methylation in both ductal carcinoma in situ and invasive breast carcinoma lesions and reduced expression of cystatin M in these tumors was confirmed by immunohistochemistry

17. strong link between CST6 promoter hypermethylation and loss of CST6 expression in breast cancer cell lines

18. Cystatin M may encode a novel epigenetically inactivated candidate tumor suppressor gene.

19. Methylation-dependent epigenetic silencing of CST6 represents an important mechanism for loss of CST6 during breast tumorigenesis and/or progression to metastasis.

20. cystatin E/M is a cervical cancer suppressor gene and that the gene is inactivated by somatic mutations and promoter hypermethylation.

Mouse (Murine) Cystatin E/M (CST6) interaction partners

1. Using quenched activity-based probes, we identified mouse cathepsin B (CtsB), which is expressed in the lower regions of the hair follicle, as an additional target of mouse Cst6

2. conclude that a tightly regulated balance between cathepsin L and cystatin M/E is essential for tissue integrity in epidermis, hair follicles, and corneal epithelium

3. cystatin M/E has a role in skin barrier formation and a potential role as a tumor suppressor gene [review]