1 Introduction
2 Quiescence in cancer: an overview
3 A molecular portrait of quiescent cancer cells
Molecular pathways and proteins involved in dormancy | Tumor type | Representative references |
---|---|---|
↑p38 MAPK, ↓ERK1/2 | Head and neck carcinoma, breast cancer, prostate cancer; melanoma; fibrosarcoma | |
uPAR/FAK/Src | Hepatocellular carcinoma | [56] |
cYES1, YAP | Colon cancer, lung cancer | |
SPARC | Prostate cancer | [59] |
TGFβ1, TGFβ2 | Prostate cancer, head and neck squamous cell carcinoma | |
NR2F1 | Head and neck squamous cell carcinoma, prostate cancer, breast cancer | |
BMP7, BMP4 | Prostate cancer, breast and lung cancer | |
CXCL12 | Breast cancer, salivary adenoid cystic carcinoma, leukemia | |
Thrombospondin | Breast cancer | [71] |
DIRAS3 (ARHI) | Ovarian cancer, breast cancer, pancreatic cancer, lung cancer | |
HIF1α | Head and neck squamous cell carcinoma, breast cancer | |
Adhesion molecules: vWF, integrins, VCAM | Breast cancer | [77] |
GAS6 | Prostate cancer | |
RAR | Head and neck squamous cell carcinoma, prostate cancer | [64] |
LIF | Breast cancer | [80] |
WNTs | Lung and breast cancer | |
Jagged 1 | Leukemia | [83] |
ZEB2 | Colorectal cancer, lung cancer | |
Anti-apoptotic factors: Bcl-xL, p-cRAF, p-ASK1 | Colorectal cancer, lung cancer; breast cancer | |
Cell cycle inhibitory factors: p27kip1, p21Cip1, p57KIP2, DYRK1A, DREAM complex | Murine leukemia, ovarian cancer, colorectal cancer | |
Stemness associated factors: Nanog, BMI1, KLF4, AXIN2, LGR5, PLAUR/CD87, CD44, ALCAM/CD166, SOX2, SOX9 | Colorectal cancer, lung cancer, head and neck squamous cell carcinoma, breast cancer, glioblastoma, melanoma, colon cancer, ovarian cancer | |
EMT-associated factors: vimentin, SNAI1/2, N-cadherin, TWIST, TG2, ZFP281, ZEB1 | Colorectal cancer, ovarian cancer, lung cancer, breast cancer | |
Autophagy associated factors: mTOR, beclin1 and VPS34, LKB1-AMPK, IGF2, VEGF, IL8, and IGF1 | Colorectal cancer, breast cancer, lung cancer, ovarian cancer, osteosarcoma | |
DNA methylation, DNA oxidation, histone modifications | Head and neck squamous cell carcinoma, prostate cancer, breast cancer, glioblastoma | |
Other epigenetic factors: KDM1B, 2, 3, 5, 6, 7; TET2 | Glioblastoma, colorectal cancer, melanoma, lung cancer, breast cancer | |
lncRNAs and miRNAs | Breast cancer | |
Embryonic-like programs (↓ cMyc↓ mTOR), morphogenesis pathways | Breast cancer, colorectal cancer, lung cancer, |
4 Differences and overlappings among dormant/quiescent cells, drug-tolerant persisters, cancer stem cells, and diapause-like and senescent cancer cells
Cellular state in cancer | Cell name | Genetic mutations | Epigenetic alterations | Primary features | Secondary features | Representative refs | |
---|---|---|---|---|---|---|---|
1 | Quiescence | QCCs DTCs | No | Yes | Slow/absent proliferation (G0 arrest) | Enhanced stemness, EMT, plasticity, drug resistance | |
2 | Persistence | DTPs | Sometimes | Yes | Drug resistance | Quiescence (most frequently), plasticity | |
3 | Stemness | CSCs | Sometimes | Yes | Tumor-repopulating capacity, self-renewal | Drug resistance, plasticity, metastatic capacity | [117] |
4 | Diapause-like | diapause-likeDTPs | No | Yes | Drug resistance | Quiescence | |
5 | Senescence | Senescent cell | No | Yes | Growth arrest (G1, sometimes G2) | SASP | [111] |