Table 1 The dysregulated TFs or signaling pathway of CSCs in distinct cancers

Head and neck squamous cell carcinoma (HNSCC)

OCT4, NANOG, FOXM1

directly knock down OCT4; inhibit DDX3 (human DEAD box RNA helicase) to achieve demethylation of m⁶A RNA in FOXM1 and NANOG

decrease radiation induced DDR and inhibit radio-sensitivity of HNSCC cell lines [30]; impair the resistance to cisplatin [99]

Breast cancer

SOX2, Wnt/β-Catenin, Hippo

use small-molecule inhibitor of neddylation MLN4924 to down-regulate SOX2; knock down YAP

suppress the formation of tumor sphere and increase sensitivity to tamoxifen [35]; reduce the expression of many Wnt target genes and hinder the initiation and growth of CSCs [77]

Hepatocellular carcinoma (HCC)

NANOG, KLF4, Wnt/β-Catenin, PPARα

knock down ABI2 to inhibit the transcription of NANOG and KLF4; use 4-phenylbutyric acid (4-PBA) to upregulate PPARα by activating β‐catenin

inhibit self-renewal and tumorigenicity of CSCs, growth and migration of HCC [38]; initiate CSCs to promote tumorigenesis [92]

Clear cell renal cell cancer

MYC

block estrogen receptor (ERβ) to target C-MYC mRNA through non-coding RNA

reduce CSC population and inhibit CSC phenotype [100]

Non-small cell lung adenocarcinoma (NSCLC)

OCT4, NANOG, Wnt/β-Catenin, STAT3, Hippo, FGF/FGFR

knock down OCT4 or NANOG or β-Catenin; apply heat shock protein (HSP) 90 inhibitors to degrade STAT3 protein; knock down YAP

decrease β-Catenin expression and the target gene CyclinD1, make cells sensitive to anticancer drugs and eliminate EMT process [79]; inhibit STAT3 mediated activation of Wnt signaling, disrupt the vitality and migration of NSCLC cells [84]; up-regulate FGFR1 transcription, inhibit self-renewal and eliminate CSC characteristics [97]

Glioblastoma (GBM)

SOX2, Notch, FGF/FGFR

knock down SOX2 or NOTCH, knock down FGFR or apply FGFR antibodies

obstruct the distribution and invasive phenotype of CSCs [80]; inhibit the expression of SOX2 and reduce tumorigenesis [96]

Prostate cancer

SOX2, NANOG, JAK/STAT, Notch, AKT

knock down IFIT5 (as interferon induced gene and downstream effector of the JAK-STAT signaling pathway) to target SOX2 and NANOG; directly knock down NOTCH1 or AKT

reduce the initiating ability of tumors and decrease prostasphere formation [83]; inhibit radiation resistance of tumor cells [87]

Esophageal squamous cell carcinoma (ESCC)

MYC, NF-κB, AKT, FGF/FGFR

activate NF-κB signaling with extracellular vesicles containing FMR1-AS1 to promote C-MYC expression; knock down AKT or FGFR2

mediate the transformation and migration of CSCs [89]; induce EMT and enrich CSC population [98]

Ovarian cancer

AKT, NF-κB, PPARα

use mono(2-ethylhexyl) phthalate (MEHP) to activate the PI3K/AKT/NF-κB pathway

promote cancer cell metastasis and induce EMT (inhibition of PPARα reverses this effect) [90]

Colorectal cancer (CRC)

SOX2, FOXM1, NANOG, PPARδ, FGF/FGFR

target RBM17 (a member of the spliceosome complex) to regulate selective splicing of FOXM1 and promote SOX2 transcription; use PPARδ agonists to induce NANOG expression; add FGFR inhibitors

enhance the stemness of CSCs and sphere formation [101]; induce CSC amplification and accelerate liver metastasis in vivo [93]; suppress self-renewal and long-term organoid [95]