Table 1.

T-type calcium channel (TTCC) expression and cellular function in melanoma. ND: not determined.

Cellular Functions of TTCCs	Cav3.1	Cav3.2	Cav3.3
Molecular Information	Human: 2377aa, O43497, chr. 17q22, CACNA1G	Human: 2353aa, O95180, chr. 16p13.3, CACNA1H	Human: 2251aa, AAM67414, chr. 22q13.1, CACNA1I
Threshold mV	−70	−70	−70
mRNA	+	+	+
Protein	IHC	IHC	ND
Functional Channels	+	+	+
Prognosis in Melanoma	Negative	Negative	ND
Expression Levels	↑ mRNA expression in melanoma cell lines and biopsies compared with melanocytes [18]	↑ mRNA expression in melanoma cell lines and biopsies compared with melanocytes [18]	↑ mRNA expression in melanoma cell lines and biopsies compared with melanocytes [18]
	Hypoxia ↑ mRNA expression (M16, JG, M28) [19]	Hypoxia ↑ mRNA expression [19]	↑ mRNA expression in BRAFV600E melanoma [20]
	↑ immunoexpression from normal skin to naevi to melanoma biopsies (tumor progression) [21]	↑ immunoexpression from normal skin to naevi to melanoma biopsies (tumor progression) [21]
	↑ immunoexpression in primary melanoma tumors with Breslow thickness >1 mm [21]	↑ immunoexpression in primary melanoma tumors with Breslow thickness >1 mm [21]
	↑ immunoexpression positively correlates with BRAFV600E protein expression and LC3 [21]	↑ immunoexpression positively correlates with Glut1 and Ki-67 [21]
	↑ mRNA expression and immunoexpression in BRAFV600E melanoma [20]
	↑ mRNA expression and immunoexpression in BRAF inhibitor-resistant melanoma [22]
	↑ mRNA expression during acquisition of Vemurafenib resistance in melanoma [22]
	↓ mRNA expression after TTCC blocker treatment in sensitive and Vemurafenib-resistant melanoma [22]
Cellular function	TTCC blocker or molecular knockdown of Cav3.1 expression arrest cells in G1 phase and decreases cell viability in melanoma cells [18,19,22]	TTCC blocker or molecular knockdown of Cav3.2 expression arrest cells in G1 phase and decreases cell viability in melanoma cells [18,19,22]	TTCC blocker arrests cells in G1 phase and decreases cell viability in melanoma cells [18,19,22]
	TTCC blocker or molecular knockdown of Cav3.1 expression impairs migration/invasion rates in BRAFV600E-mutant melanoma cells [20]	TTCC blocker or molecular knockdown of Cav3.2 expression impairs migration/invasion rates in BRAFV600E-mutant melanoma cells [20]	TTCC blocker impairs migration/invasion rates in BRAFV600E-mutant melanoma cells [20]
	TTCC blocker reduces tumor growth in vivo [5]	TTCC blocker reduces cell viability and inhibit migration/invasion rates in Vemurafenib-resistant melanoma cells [20]	TTCC blocker reduces cell viability and inhibit migration/invasion rates in Vemurafenib-resistant melanoma cells [20]
	TTCC blocker reduce cell viability and inhibit migration/invasion rates in Vemurafenib-resistant melanoma cells [20]	TTCC blocker reduce tumor growth in vivo [22]	TTCC blocker reduce tumor growth in vivo [22]
Relative to Autophagy	TTCC blocker or molecular knockdown of Cav3.1 blocks autophagy flux in all melanoma cells [19,20,22]	TTCC blocker or molecular knockdown of Cav3.2 blocks autophagy flux in all melanoma cells [19,20,22]	TTCC blockade inhibits autophagy flux in all melanoma cells [19,20,22]
	TTCC blocker inhibit autophagy flux in Vemurafenib-resistant melanoma cells [22]	TTCC blocker inhibit autophagy flux in Vemurafenib-resistant melanoma cells [22]	TTCC blocker inhibit autophagy flux in Vemurafenib-resistant melanoma cells [22]