Table 2.

Roles of cystatin M/E (CST6) in cancer—a short summary.

Tumor Type	Tumor-Suppressive	Tumor-Promoting	References
Breast cancer	Ectopic expression of CST6 reduces cell growth, proliferation, migration, invasion in vitro and in vivo. Patients with methylated CST6 have a worse disease-free and overall survival rate	Increased expression in breast cancer cells. Overexpression of cystatin M/E in TNBC tissues is associated with a low disease-free survival rate	[72,73,74,85,86,114,115]
Cervical cancer	Loss of cystatin M/E in primary tumors. CST6 re-expression inhibits tumor cell growth		[100]
Cutaneous squamous cell carcinoma (cSCC)	cSCC metastasis is partly attributed to a decrease in cystatin M/E expression	Overexpression of CST6 in cSCC tissues vs adjacent normal skin	[105,106]
Gastric cancer	Shorter survival time for patients with methylated CST6 promoter		[110,111]
Glioma	Reduction of cell motility and invasion after CST6 overexpression		[102]
Hepatocellular carcinoma		Increased cystatin M/E expression is correlated with poor survival of HCC patients	[116]
Lung cancer	CST6 ectopic expression suppresses NSCLC cell lines growth		[98]
Melanoma	CST6 involved in the suppression of proliferation, migration and metastasis of melanoma cells		[42,107,108]
Oral cancer		CST6 is overexpressed in oropharyngeal metastatic cells. Its silencing increases cell proliferation and invasion	[117,118]
Pancreatic cancer		Cystatin M/E expression is associated with PDAC cells growth and proliferation	[119]
Papillary thyroid carcinoma (PTC)		Increase of CST6 in PTC is associated with lymph node metastasis	[120]
Prostate cancer	Overexpression of cystatin M/E inhibits cell growth and lung metastasis incidence		[109]
Renal cell carcinoma (RCC)	Promoter hypermethylation of CST6 is associated with a shortened progression-free and overall survival of patients with metastasized RCC		[112,113]