Table 1.

NT2/D1 cells as a biological model of CSCs

Intervention/animal model	Characterization	References
In vitro
17β-estradiol, ERβ-selective agonist (DPN, PPT)	- ↑Migration, invasion and anchorage‑independent growth	[60]
Activin A, BMP4	- Activin A → ↑pluripotency, TGF-β, Notch, TP53, and Hippo signalling - BMP4 → ↑TGF-β, pluripotency, Hippo and Wnt signalling	[61]
piR-36249, DHX36	- piR-36249 and DHX36 inhibit the malignant phenotype of testicular cancer cells by ↑OAS2 protein	[62]
phorbol 12-myristate 13-acetate (PMA)	- ↑miR-630 → ↓NANOG	[63]
Retinoic acid	- Opposite Insulin-like growth factor 1 receptor (IGF-1R) and miR-6165 pattern	[64]
No intervention	- ↑Anterior gradient-2 (AGR2) → ↑proliferation, ↑invasion, ↑glycolysis	[65]
	- SOX9/TRPC3 promotes proliferation and controls cell morphology	[66]
	- E2 activate ESR1/ESR2 → ↑number and viability	[67]
	- Endogenous HER2-miR1 found in NT2 → ↓Wnt signaling	[68]
	- ↓miR-196a-5p	[69]
	- ↓TIG1 and SPINK2 - TIG1 inhibited cell invasion, migration, and epithelial–mesenchymal transition (EMT) through uPA/uPAR signaling pathway - SPINK2 augments TIG1 functions	[70]
	- Short-term activation of WNT signaling induced a differentiation - WNT signaling is distinct among types of germ cell tumors	[71]
	- ↑HOTTIP → ↑cell proliferation - HOTTIP binds to miR-128-3p to regulate HOXA13 expression	[72]
	- ↑Citric acid cycle/mitochondrial oxidative phosphorylation - ↑Sphingolipid biosynthesis	[73]
	- Loss of functions of HOXA10 → ↑proliferation of testicular cancer cells	[74]
	- DNA methylation promotes PIWI-LIKE 2 expression	[75]
	- ↑SOX2OT expression	[76]
	- Oxidative stress increased LRWD1 expression through a Nrf2-dependent mechanism	[77]
	- SPRY4 and SPRY4-IT1 may be oncogenes through activation of the PI3 K/Akt pathway	[78]
	- OCT4 A and OCT4B2 have similar expression - ↑OCT4B2 transcription after heat shock	[79]
	- DLK1–MEG3 locus drives the tumorigenicity - 5-azaD suppresses DLK1	[80]
	- Activation of PPARβ/δ inhibits RAR/RXR dimerization and tumor proliferation	[81]
	- SOX2 overexpression promote speed, mode and path of cell migration, but not the adhesion ability - ↑Expressions of tumor suppressor protein TP53 and the HDM2 oncogene	[82]
	- ↑SOX2 expression - Down-regulation of SOX2 promotes apoptosis - Inhibition of OCT3/4 induces differentiation	[83]
	- NF-Y-induced inhibition of cell growth is p53-independent	[56]
In vivo
Mouse	- Keratin, vimentin, neurofilament proteins and desmin	[15]
	- ↑SOX2 expression	[83]