Table 2

Tumor-inhibiting and tumor-promoting genes induced in senescent tumor cells

GeneSenescent cells/inducerReference
Intracellular growth inhibitors
p21Waf1/Cip1/Sdi1 (pleiotropic CDK inhibitor)Different tumor cell lines/various drugs and radiation (31 , 42 , 48 , 49)
p16Ink4A (CDK4/6 inhibitor; tumor suppressor)K562 leukemia/hydroxyurea; murine Eμ-myc lymphoma/cyclophosphamide (42 , 60)
p27Kip1 (CDK2 inhibitor)K562 leukemia/hydroxyurea (42)
BTG1 (tumor suppressor)HCT116 colon caa/doxorubicin (49)
BTG2 (BTG1-related)HCT116 colon ca/doxorubicin (49)
 EPLIN (actin-binding protein; putative tumor suppressor)HCT116 colon ca/doxorubicin (49 , 56)
MCF-7 breast ca/retinoids
FAT10 (ubiquitin family)MCF-7 breast ca/retinoids (56)
Secreted and cell-surface-associated tumor-inhibiting proteins
IGFBP-3 (IGF-binding protein; cytostatic; apoptogenic)HeLa cervical ca/bromodeoxyuridine; MCF-7 breast ca/retinoids (48 , 56)
IGFBP-6 (IGF-binding protein; cytostatic)HCT116 colon ca/doxorubicin (49)
IGFBP-4 (IGF-binding protein; cytostatic)HeLa cervical ca/bromodeoxyuridine (48)
Maspin (serine protease inhibitor; inhibits invasion and angiogenesis; tumor suppressor)HCT116 colon ca/doxorubicin (49)
MIC-1 (TGF-β family)HCT116 colon ca/doxorubicin (49)
βig-H3 (ECM protein; inhibits tumorigenesis)HeLa cervical ca/bromodeoxyuridine; MCF-7 breast ca/retinoids (48 , 56)
Secreted and cell-surface-associated tumor-promoting proteins
TGFα (mitogen; EGFR ligand)HCT116 colon ca/doxorubicin (49)
Cyr61 (angiogenic; mitogenic)HCT116 colon ca/doxorubicin (49)
CTGF (Cyr61-related; angiogenic; mitogenic)HT1080 fibrosarcoma/p21 (4)
Epithelin/granulin (mitogenic)HT1080 fibrosarcoma/p21 (4)
Galectin-3 (antiapoptotic)HT1080 fibrosarcoma/p21 (4)
Prosaposin (antiapoptotic)HT1080 fibrosarcoma/p21 (4 , 49)
HCT116 colon ca/doxorubicin
 βAPP (Alzheimer’s β amyloid precursor; mitogenic)HT1080 fibrosarcoma/p21 (4 , 49)
HCT116 colon ca/doxorubicin
Cathepsin B (serine protease; promotes invasion)HT1080 fibrosarcoma/p21 (4)
Plasminogen activator inhibitor-1 (serine protease inhibitor; promotes angiogenesis and invasion)HeLa cervical ca/bromodeoxyuridine; HT1080 fibrosarcoma/p21 (4 , 48)
Dual-function growth regulators
Amphiregulin (EGF family; mitogenic in normal cells; antimitogenic in tumor cells)HCT116 colon ca/doxorubicin (49)
Activin A (TGF-β family)HT1080 fibrosarcoma/p21 (4)
CD44 (cell adhesion molecule; pleiotropic growth modulator)HCT116 colon ca/doxorubicin (49)
Jagged-1 (Notch receptor; stem cell growth regulator; angiogenic)HCT116 colon ca/doxorubicin (49)
  • a ca, carcinoma; EGF, epidermal growth factor; EGFR, EGF receptor.