ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer
Abstract
:1. Introduction
2. Overview of the RAS/RAF/MEK/ERK1/2 Signaling Pathway
3. Targeting the Oncogenic Activation of the RAS/RAF/MEK/ERK Signaling for Cancer Therapy
3.1. Roles of ERK Signaling in Proliferation and Survival
3.2. Roles of ERK Signaling in Tumor Development
3.3. Oncogenic Activation of ERK1/2 in Human Cancers
3.4. Anticancer Agents Targeting the ERK Cascade
4. Role for the ERK Cascade in Apoptosis
4.1. Compounds/Stimuli That Induce Apoptosis through ERK Activation
4.2. Mechanisms of ERK-Induced Apoptosis
4.3. DNA Damage and p53 in the ERK Activation-Induced Apoptosis
4.4. ROS and ERK Activation-Induced Cell Death
4.5. DUSP and Negative Regulators of the ERK Cascade in the ERK Activation-Induced Cell Death
4.6. Kinetics and Distribution of Phosphorylated ERK and Cell Death
4.7. The Cellular Threshold for ERK-Dependent Cell Death
4.8. ERK Activation and Other Types of Cell Death
5. Conclusions and Perspectives: Promises and Challenges for ERK-Induced Apoptosis in Cancer
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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In Vivo/Cellular Model | Stimuli Inducing Cell Death | Detected Time Points of Activated ERK | Timing of Evaluating Cell Death | Characteristics of Cell Death | Evidence Implicating MEK–ERK in Cell Death | p53- Dependent | p53 Activation | ROS Induction | Reference |
---|---|---|---|---|---|---|---|---|---|
RPTEC/TERT1 cells, Mouse renal proximal tubular cells | Cisplatin | 72 h | 48, 72 h | Caspase-3, Bcl-2, Anneexin V, Propidium iodide (PI) | Panduratin A | no information | no information | YES | [87] |
Nasopharyngeal carcinoma (NPC) cell line (NPC-039 and NPC-BM) | Dehydrocrenatidine | 24 h | 24 h | Caspase-3, -8, -9, Bak, Bax, Bcl-xL, Bcl-2, PARP | U0126 | no information | no information | NO | [88] |
Human proximal tubular cell (HK-2) | Urinary proteins | 2, 8 h | 48 h | Annexin V | U0126 | no information | no information | YES | [89] |
Mouse auditory cell line (HEI-OC1) | Cisplatin | 24 h | 24 h | Caspase-3, TUNEL, LC3-II | U0126 | no information | no information | YES | [90] |
Human endometrial cancer (EC) cell (Ishikawa, HEC-1A) | Curcusone C | 24 h | 24 h | Caspase-3, -9 | U0126 | no information | no information | no information | [91] |
T24 | Pterostilbene, Cisplatin, Gemcitabine | 48 h | 48 h | LC3-II, β-galactosidase (senescence) | U0126 | NO | no information | no information | [92] |
Human non-small cell lung cancer (NSCLC) cell (A549, NCI-H292) | Morusin | 1, 2, 4, 8, 12, 24 h | 48 h | Caspase-3, PARP, LC3-II, | U0126 | no information | no information | YES | [93] |
Human umbilical vein endothelial cells (HUVECs) | Death-domain associated protein (DAXX) and inorganic phosphate (Pi) | 1 h | 24 h | Caspase-3 | U0126 | no information | no information | no information | [94] |
LNCaP and PC-3 cells | γ-tocotrienol (GT3) | 6 h | 12 h | Caspase-3, -9 | U0126 | no information | no information | no information | [95] |
Human gastric cancer cell lines (SGC-7901, BGC-823) | Ginsenoside Rg5 | 24 h | 24 h | Caspase-3, -8, -9, PARP, LC3-II | U0126 | no information | no information | YES | [96] |
A549 | Derrone (DR) | 3, 6, 12, 24 h | 24 h | Caspase-3, -8, PARP, LC3-II | U0126 | YES | no information | YES | [97] |
Human colorectal cancer cells (HCT116 p53+/+ and p53−/−) | 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) | 6, 12, 18, 24, 36, 48 h | 48 h | Caspase-3, PARP | U0126 | NO | no information | no information | [98] |
HeLa | HVJ-E infection | 24 h | 24 h | Caspase-3, -9, LC3-II | U0126 | no information | no information | no information | [99] |
RSC96 | Mesenchymal stem cells (MSC)-derived extracellular vesicles (EVs) | 24 h | 24 h | Annexin V, Bcl-2, Bax | U0126 | no information | no information | no information | [100] |
HL-60 | Platinum complex containing a piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = piplartine demethylated derivative; and PPh3 = triphenylphosphine) | no infromation | 24, 48 h | Annexin V, Caspase-3 | U0126 | no information | no information | YES | [101] |
Non-small cell lung cancer (NSCLC) cells (H1975, A549) | M. tenacissima extract (MTE) | 24 h | 24 h | Caspase-3, PARP, LC3-II | U0126 | no information | no information | no information | [102] |
Non-small cell lung cancer (NSCLC) cells (PC9, H1975) | Scutellarin | 48 h | 24, 48 h | Annexin V, LC3-II | U0126 | no information | no information | no information | [103] |
Colon cancer cell lines (SW480, SW620, DLD-1) | NSC95397 | 6 h | 24 h | Caspase-3, -7, -9, PARP | U0126 | NO | no information | no information | [104] |
Human breast cancer cell line (MDA-MB-231) | Triptolide | 2, 4, 8, 24, 48 h | 48, 72 h | Caspase-3, PARP | U0126 | no information | no information | YES | [37] |
Human breast cancer cell (MCF-7) | Triptolide (TPI) | 24 h | 24 h | Caspase-3, LC3-II | U0126 | no information | no information | no information | [105] |
MKN45 | Alpha, 2′-dihydroxy-4,4′-dimethoxydihydrochalcone | 48 h | 48 h | Annexin V, LC3-II | U0126 | no information | no information | YES | [106] |
Non-small cell lung carcinoma (NSCLC) (A549, H226, H1299) | Artocarpin | 0.5, 1, 2, 3, 4 h | 6, 24 h | Caspase-3 | U0126, SB202190 | dependent and independent | YES | YES | [107] |
Murine macrophage cell line RAW264.7 | H. pylori secreted protein HP1286 | 15, 30, 60, 90, 120 m | 24 h | Caspase-3 | U0126 | no information | no information | no information | [108] |
HepG2 | Cholix toxin (Cholix) | 4, 8, 12 h | 12 h | Caspase-3, -9 | U0126, SB20852, SP600125 | no information | no information | YES | [109] |
Human ovarian cancer cell lines (HEY, A2780) | Baicalein (BA) | 24 h | 24 h | LC3-II, PARP | U0126, ERK siRNA | no information | no information | no information | [110] |
MGC-803 | Equol | 12, 24, 48 h | 24 h | Caspase-3, PARP, cIAP1 | U0126 | no information | no information | no information | [111] |
A549 | Derivatives of 6-cinnamamido-quinoline-4-carboxamide (CiQ) | 8 h | 48 h | Caspase-9, PARP, LC3-II | U0126, dominant-negative MEK1 | NO | no information | no information | [112] |
Human nasopharyngeal carcinoma (NPC) cell lines (HONE-1, NPC-039) | Polyphyllin G (polyphyllin VII) | 3, 6, 12 h | 24 h | Caspase-8, -3, -9, Bax, Bcl-xL, Bcl-2, LC3-II | U0126 | no information | no information | no information | [113] |
253J-Bv, T24 | Co-treatment of curcumin and cisplatin | 3, 6, 24 h | 24 h | Caspase-3, Anneexin V | U0126 | dependent and independent | YES | YES | [114] |
Burkitt’s lymphoma Ramos cells | MytiLec | 12, 24 h | 24 h | Caspase-3, -9, Annexin V | U0126 | no information | no information | no information | [115] |
Human umbilical vein endothelial cells (HUVECs) (SGC7901) | farrerol | 24 h | 24 h | G0/G1 cell cycle arrest | U0126 | no information | no information | no information | [116] |
Osteoblasts (OBs) | Cadmium (Cd) | 2, 3, 4, 5, 6 h | 24 h | Bax, Bcl-2, Caspase-3, -9, PARP | U0126 | no information | no information | Decrease in ROS generation | [117] |
HCT116 | Physalin B | 12, 24, 36 h | 24 h | Caspase-3, PARP, LC3-II | U0126 | no information | no information | YES | [118] |
NIH/3T3 | Paraquat | 0.5, 1, 6, 12, 24 h | 24 h | Cytochrome c | U0126 | no information | no information | YES | [119] |
Breast cancer cell lines (MCF-7, BT474, MDA-MB-231, SUM1315) | D Rhamnose β-hederin (DRβ-H) | 5, 30 m, 2, 6, 48 h | 48 h | Annexin V, caspase-3, -8, -9 | U0126 | no information | no information | no information | [120] |
A549 | Pyocyanin (PCN) | 5 m, 1, 3, 6, 12, 24 h | 24 h | Caspase-3 | U0126 | no information | no information | YES | [121] |
Mouse TM4 Sertoli cells | Nonylphenol (NP) | 15, 30, 60, 180 m | 24 h | Sub G1, Caspase-3, PARP, Bcl-2, Bax | U0126 | no information | no information | YES | [122] |
HT-29 | Piperlongumine (PPLGM) | 5, 10, 15, 30, 60 m | 24 h | Caspase-3 | U0126 | no information | no information | no information | [16] |
BRL 3A | Cadmium (Cd) | 12 h | 12 h | Annexin V, Bax, Bcl-2 | U0126 | no information | no information | YES | [123] |
Rat liver cells | Corticotrophin-releasing hormone (CRH) | 8 h | 8, 24 h | Bax, Bcl-2 | U0126 | no information | YES | no information | [124] |
MDA-MB-468 | Allyl isothiocyanate (AITC) | 2 h | 12 h | Caspase-3, -9, Bcl-2, Cytochrome c | U0126 | NO | NO | YES | [125] |
Mouse embryonic stem (mES) cells | Sodium nitroprusside (SNP) | 4, 8, 12, 24 h | 24 h | Caspase-3, -8, -9, Annexin V | U0126 | no information | no information | YES | [126] |
SGC-7901 | β,β-Dimethylacrylshikonin | 2, 4, 8, 12, 24 h | 48 h | Caspase-3, -8, -9, Bax, Bcl-xL, Bcl-2, PARP, Cytochrome c | U0126 | no information | no information | no information | [127] |
H9c2 | Cyclosporine A (CsA) | 0.25, 0.5, 1, 4, 8, 12, 24 h | 4 h | Caspase-3, Bax, Bcl-2, Annexin V, TUNEL | U0126 | no information | no information | no information | [128] |
Breast cancer cell lines (MDA-MB-231, KPL-3C) | Olaparib | 1, 12 h | 12, 24 h | Annexin V | U0126 | no information | no information | no information | [129] |
Jurkat/NTAL(+) | Methylprednisolone | 5, 30 m | 24 h | Annexin V, Propidium iodide (PI) | U0126 | no information | no information | no information | [130] |
Jurkat | Phorbol myristate acetate (PMA) | 24 h | 16, 24 h | DNA fragmentation | U0126, PD98059 | no information | no information | no information | [131] |
Head kidney macrophage (HKM) | Arsenic | 24 h | 24 h | Caspase-3 | U0126 | no information | no information | YES | [132] |
LLC-PK1 | Cysteinyl leukotrienes (cysLTs) synthesis | 0.5, 1, 3, 6, 12, 24 h | 24 h | Caspase-3, Bax, Bcl-2, Cytochrome C | U0126 | no information | no information | no information | [133] |
HeLa | Phenethyl isothiocyanate (PEITC) | 8, 24 h | 24 h | Caspase-3, PARP | U0126 | no information | no information | no information | [134] |
Human lung adenocarcinoma A549 | Pemetrexed | 4, 8, 12, 24, 48 h | 72 h | Caspase-3, TUNEL | U0126, PD98059, ERK siRNA | no information | no information | no information | [135] |
Human endometrial cancer Hec1A | Icaritin | 3, 6, 12, 24 h | 24 h | Caspase-3, -9, PARP, Cytochrome c, TUNEL, Annexin V | U0126 | no information | no information | no information | [23] |
Breast cancer MDA-MB-453 and MCF7 | Icaritin | 5, 15, 30 m, 1, 2, 4, 8, 12, 24 h | 48 h | Bcl-2, PARP, Annexin V | U0126 | no information | no information | no information | [136] |
Renal tubular epithelial cell (RTEC) | HIV-1 viral protein r (Vpr) | 5 d | 5 d | Caspase-3, -8, -9, PARP | U0126 | no information | no information | no information | [137] |
Spinal cord | Spinal cord ischemia/Reperfusion (I/R) injury | 3 h | 24 h | Caspase-3, TUNEL, c-IAP2 | U0126 | no information | no information | no information | [138] |
HL-60, U397, SK-MEL-1 | Asteriscunolide A (AS) | 0.5, 1, 2, 3 h | 24 h | Caspase-3, -7, -9, PARP | U0126, PD98059 | no information | no information | YES | [139] |
Astrocytes | Glutamate | 3, 6, 9 h | 24 h | Caspase-3, TUNEL | U0126, DUSP5, 6 over-expression | no information | no information | no information | [82] |
Neuro-2a | 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) | 0.5, 1, 2, 4, 6, 8 h | 24 h | Sub-G1, Caspase-3, -7, -9, -12, Bax, Bcl-2, PARP, Cytochrome c | PD98059 | no information | no information | no information | [140] |
Human platelets | Bisdemethoxycurcumin (BDMC) | 1, 2 h | 1 h | Caspase-3, -8, -9, Bax, BID, Bcl-2, Bcl-xL, Cytochrome c | PD98059 | no information | no information | YES | [141] |
HeLa, MCF-7 | N-Methyl and N,N-dimethyl bis(indolyl)hydrazide-hydrazone analog derivatives | no information | 24 h | Bak | PD98059 | YES | YES | YES | [142] |
Human ovary adenocarcinoma (SKOV3) | CRT1 (Ent-18-acetoxy-7β-hydroxy kaur-15-oxo-16-ene) | 24 h | 24 h | Caspase-3, -7, -9, PARP, Cytochrome c, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [143] |
Human pulmonary microvascular endothelial cells (HPMECs) | Cigarette smoke extract (CSE) | 12 h | 12 h | Caspase-3, TUNEL, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [144] |
Hepatocellular carcinoma (HCC) (SMMC7721, Bel7402) | Hispidulin | 48 h | 48 h | Caspase-3, Bax, Bcl-2, Annexin V, Propidium iodide (PI), TUNEL | PD98059 | no information | no information | no information | [145] |
Human osteosarcoma cells (HOS) | Honokiol (HNK) | 24 h | 24 h | Caspase-3, -9, Bcl-2, Bcl-xL, survivin, PARP, Annexin V, Propidium iodide (PI), TUNEL | PD98059 | no information | no information | YES | [146] |
Human hepatoma (Hep3B) | Desipramine | 1, 2, 4, 8 h | 24 h | LDH | PD98059 | no information | no information | YES | [147] |
Human neuroblastoma (SH-SY5Y) | Cearoin | 12 h | 12 h | Caspase-3, Bax, Bcl-2, PARP | PD98059 | no information | no information | YES | [148] |
Human Glioma (U87) | Valproic acid (VPA) | 72 h | 72 h | Hoechst 33342, Caspase-3, -9, Bax, Bcl-2, Cytochrome c, TUNEL, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [149] |
Human gastric cancer cells (AGS) | Agrimonolide (AM) | 24 h | 24 h | Caspase-3, -8, -9, Bax, Bcl-2, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | YES | [150] |
β-cell-derived cells (RIN-m5F) | Etoposide | 15, 30, 60 m | 24 h | SubG1, Caspase-3, -6, -7, -9, Cytochrome c, Bax, Bcl-2, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [19] |
HT-29 | Simvastatin | 24 h | 48 h | Caspase-3, Bax, Bcl-2 | PD98059 | no information | no information | no information | [151] |
Ardiac myocytes (H9c2) | Doxorubicin (DOX) | 2, 6, 12, 24, 48 h | 24 h, 48 h | TUNEL, Annexin V, Propidium iodide (PI) | PD98059, ERK siRNA | YES | YES | no information | [152] |
RAW 264.7 cells | Cypermethrin | 15, 30 m | 48 h | Annexin V, Propidium iodide (PI) | PD98059 | no information | YES | YES | [153] |
Male Sprague–Dawley rats, Primary hippocampal neuron cells | Early brain injury (EBI) following subarachnoid hemorrhage (SAH), oxyhemoglobin (OxyHb) | 6, 12, 24, 48 h | 24 h | Caspase-3, -8, -9, PARP, TUNEL | PD98059 | YES | YES | YES | [154] |
Neuroblastoma cells (neuro-2a) | Honokiol (HNK) | 48, 72 h | 72 h | BrdU | PD98059 | no information | no information | YES | [155] |
Human extravillous cytotrophoblast (EVCT)-derived cells (HTR-8/SVneo, HPT-8) | Coplanar polychlorinated biphenyls (Co-PCBs) | 24 h | 24 h | Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [156] |
Human multiple myeloma (MM) cells (U266) | Cinobufagin (CBG) | 3 h | 24 h | Caspase-3, Bcl-xL, Bcl-2, PARP, Survivin, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | YES | [157] |
Lung adenocarcinoma cells (A549) | Triptolide (TP)/Hydroxycamptothecin (HCPT) | 24 h | 24 h | Caspase-3, -9, Cytochrome c, Bax, Bcl-2, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [158] |
Human leukemia cells (HL-60) | Bromo analogue (TBr) | 6, 12, 24 h | 24 h | Caspase-3, -8, -9, PARP, Bax, BID, Bcl-2, Sub-G1, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [159] |
Human alveolar cells (A549) | Acetochlor (ACETO) | 6, 12, 24, 48 h | 72 h | Caspase-3, -9, PARP, Bak, Bax, BID, Bad, MCL-1, Bcl-xL, Bcl-2, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | YES | [160] |
PC12 | Perfluorohexanesulfonate (PFHxS) | 0.5, 1, 3, 6, 9, 16, 24 h | 24 h | Caspase-3, Propidium iodide (PI), TUNEL | PD98059 | no information | no information | YES | [161] |
Prostate cancer cells (PC3) | MHY-449 | 24 h | 24 h | Caspase-3, -8, Bax, Bcl-2, PARP, Annexin V, Propidium iodide (PI) | PD98059 | NO | no information | no information | [162] |
Neuro-2a | As2O3 | 15, 30, 60 m | 24 h | Caspase-3, -6, -7, -9, -12, PARP, Bax, Bcl-2, | PD98059 | no information | no information | YES | [163] |
Gastric cancer cells (SGC7901, MGC803) | Interferon-α (IFN-α)/5’-Deoxy-5-fluorouracil (5’-DFUR) | 24, 48 h | 24 h, 48 h | Caspase-3, -9, PARP | PD98059, ERK siRNA | no information | no information | no information | [164] |
Osteosarcoma cells (G292) | Capsaicin | 2, 6 h | 24 h | Caspase-9, Annexin-V | PD98059 | no information | no information | no information | [165] |
Rat chondrocyte | Mechanical stress (0.5 MPa) | 24 h | 24 h | Caspase-3, -9, Bax, Bcl-2, Annexin V, Propidium iodide (PI), TUNEL | PD98059 | no information | no information | no information | [166] |
Leukemia cells (KBM-5) | Tanshinone IIA (Tan IIA) | 6, 12, 18, 24 h | 24 h | Sub-G1, PARP | PD184352 | no information | no information | no information | [85] |
Rat hepatic stellate cell (HSC-T6) | Tanshinone IIA (Tan IIA) | 6 h | 24 h | Sub-G1, Caspase-3, -9, PARP, Bax, Bcl-2 | PD98059 | no information | no information | YES | [167] |
Cerebellar granule cells (CGCs) | Perfluorooctane sulfonate (PFOS) | 5, 10, 15, 30 m, 1, 3, 6 h | 24 h | Hoechst 33342, Caspase-3 | PD98059 | no information | no information | no information | [168] |
Human oral squamous cell carcinomas (YD-10B) | Fomitoside-K | 4, 8, 12, 24 h | 24 h | Caspase-3, -9, PARP, Bax, Bcl-2, Survivin, Propidium iodide (PI) | PD98059 | no information | no information | YES | [169] |
Human myeloid leukemia cells (K562) | Calactin | 6, 12, 24 h | 12 h, 24 h | Caspase-3, -8, Caspase-9, Bax, Bcl-2, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [170] |
Human gastric cancer cells (CS12) | Euphol | 4, 24, 48, 72 h | 48 h, 72 h | Caspase-3, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [171] |
Human oral squamous cell carcinoma (OSCC) cells (YD-8) | P. densiflora leaf essential oil (PLEO) | 4, 8 h | 8 h | Caspase-9, PARP, Bax, Bcl-2 | PD98059 | no information | no information | YES | [172] |
Osteoblasts (Saos-2) | CdCl2 | 3, 4, 18 h | 48 h, 72 h | APO Percentage dye | PD98059 | no information | no information | no information | [173] |
Human hepatoma (HepG2) | ZL11n | 24 h | 24 h | Caspase-3, Bax, Bcl-2, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [174] |
Amygdala region in SPS rats | Single-prolonged stress (SPS) | 1 h | 1 h, 7 d | Bax, Bcl-2, TUNEL | PD98059 | no information | no information | no information | [175] |
Human myeloid leukemia cells (K562) | Ormeloxifen (ORM) | 1, 3, 6, 24 h | 48 h | Caspase-3, -9, Bax, Bcl-2, Annexin V, Propidium iodide (PI), TUNEL | PD98059 | no information | no information | no information | [176] |
HK-2 | Cyclosporine A (CyA) | 1, 3, 6, 24 h | 24 h | Hoechst 33258 | PD98059 | no information | no information | no information | [177] |
PC12 | Parathyroid hormone (PTH) | 24, 48, 72 h | 24, 48, 72, 96 h | Caspase-3, Propidium iodide (PI), DNA ladder | PD98059 | no information | no information | no information | [178] |
HCT116 | Qizhen capsule (QZC) | 15, 30, 60 m | 24 h, 48 h | Caspase-3, -9, Bax, Bcl-2, PARP, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | no information | [179] |
Human melanoma cells (A375SM), mouse xenograft model | Shikonin | 24 h | 24 h | Bax, Bcl-2, PARP, Annexin V, propidium iodide (PI), TUNEL | no information | no information | no information | no information | [180] |
Rat hepatocytes | Di-(2-ethylhexyl)phthalate (DEHP) | 24 h | 24 h | Caspase-3, PARP, Bad, Bax, Bcl-2, Bcl-xL, Annexin V, Propidium iodide (PI) | PD98059 | no information | no information | YES (ROS independent) | [181] |
Human leukemia cell line (K562) | Prodigiosin | 48 h | 24, 48 h | Caspase-3, -8, -9, Annexin V, LC-3 | PD184352 | no information | no information | YES | [86] |
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Sugiura, R.; Satoh, R.; Takasaki, T. ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer. Cells 2021, 10, 2509. https://doi.org/10.3390/cells10102509
Sugiura R, Satoh R, Takasaki T. ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer. Cells. 2021; 10(10):2509. https://doi.org/10.3390/cells10102509
Chicago/Turabian StyleSugiura, Reiko, Ryosuke Satoh, and Teruaki Takasaki. 2021. "ERK: A Double-Edged Sword in Cancer. ERK-Dependent Apoptosis as a Potential Therapeutic Strategy for Cancer" Cells 10, no. 10: 2509. https://doi.org/10.3390/cells10102509