Roles of cancer stem cells in gastrointestinal cancers

Table 1 Methods for targeting liver cancer stem cells in the treatment of liver cancer

Ref.	Genes/transcription factors/protein	Inducing way	Role
Park et al[43]	EpCAM-high HCC stem cells	Upregulating CEACAM1	Promoting the growth of LC
Deng et al[44]	Histone demethylase JMJD2D	Enhancing Sox9 expression	Promoting the growth of LC
Yang et al[45]	lncARSR	Targeting STAT3 signaling	Promoting LCSCs expansion
Chen et al[47]	4-PBA	Activating β-catenin signaling pathway	Promoting the growth of LC
Galizia et al[49]	CD133	-	Indicator of tumor recurrence
Haraguchi et al[51]	CD13	-	Causing drug resistance of LCSCs
Yang et al[52]	OV6	-	Causing drug resistance of LCSCs
Wei et al[53]	CD44	Regulating PES1	Promoting the growth of LC
Chen et al[55]	FOXM1	Reducing the expression of ALDH2	Inducing the apoptosis of LCSCs
Dou et al[56]	BC-02	Inhibiting CD13	Eradicate LCSCs
Zhou et al[57]	CD133-apt-Dox	Targeting CD133-expressing cells	Inhibiting the growth of LC
Feng et al[58]	MiR-124	-	Inhibiting LCSCs self-renewal
Jiang et al[59]	MiR-365	Regulating RAC1 pathway	Inhibiting the proliferation and invasion of HCC cells
Li et al[60]	MicroRNA-21	-	Inhibiting highly invade LCSCs
Si et al[61]	MiR-219	E-cadherin pathway	regulates the expansion of LCSCs
Dou et al[62]	MicroRNA-6838-5p	Down-regulating CBX4 expression and Inactivating ERK signaling	Inhibiting self-renewal and metastasis of Human LCSCs
Zhang et al[63]	MiR-589-5p	Inhibiting MAP3K8	Inhibiting the growth of LC
Wang et al[64]	HAND2-AS1	-	Promoting the growth of LC
Li et al[66]	Neuropilin1	The loss of neuropilin1	Inhibiting LCSCs
Wang et al[67]	ZBP-89	Inhibiting Notch1 signaling pathway	Regulating self-renewal of LCSCs

HCC: Hepatocellular carcinoma; LC: Liver cancer; LCSCs: Liver cancer stem cells.

Table 2 Methods for targeting colorectal cancer stem cells in the treatment of colorectal cancer

Ref.	Genes/transcription factors/protein	Inducing way	Role
Fumagalli et al[72]	Lgr5	-	Promoting the growth of CRC
Cheung et al[74]	CD16	-	Promoting the growth of CRC
Razi et al[75]	DCLK1	MiR-137 and Mir-15a-dependent manner	Promoting the growth of CRC
Park et al[76]	JAK2/STAT3/CCND2 axis	-	Causing drug resistance of CCSCs
Liu et al[77]	Sec62	Activating the Wnt/β-catenin pathway	Causing drug resistance of CCSCs
Izumi et al[78]	F-Box/WD repeat-containing protein 7	-	Causing drug resistance of CCSCs
Wei et al[79]	PD-L1	Activating HMGA1-dependent Signaling pathway	Maintaining CSCs self-renewal
Cho et al[80]	5-FU	Activing p53-mediated WNT/β-catenin pathway	Promoting the stemness of CRC
Chen et al[81]	Phenethyl isothiocyanate	Suppressing Wnt/β-catenin pathway	Inhibiting CCSCs
Chen et al[82]	(-)-Epigallocatechin-3-Gallate	Suppressing Wnt/β-catenin pathway	Inhibiting CCSCs
Dahal et al[83]	AGR2	Regulating Wnt/β-catenin pathway	Regulating the stemness maintenance of CCSCs
Jang et al[84]	Tankyrase inhibitors	Downregulating c-KIT tyrosine kinase	Inhibiting the growth of CD44-positive CCSCs
Liu et al[85]	PTK6 interacts with JAK2	Activating JAK2/STAT3 signaling	Reversing chemoresistance in CRC
Quarni et al[86]	Mitramycin A	-	Inhibiting CCSCs
Lim et al[88]	PrPC	Interacting with c-MET	Inhibiting CCSCs

CCSC: Colorectal cancer stem cells; CRC: Colorectal cancer; CSCs: Cancer stem cells.