Platinum-based chemotherapeutics represent a mainstay of cancer therapy, but resistance limits their curative potential. Through a kinome RNAi screen, we identified microtubule-associated serine/threonine kinase 1 (MAST1) as a main driver of cisplatin resistance in human cancers. Mechanistically, cisplatin but no other DNA-damaging agents inhibit the MAPK pathway by dissociating cRaf from MEK1, while MAST1 replaces cRaf to reactivate the MAPK pathway in a cRaf-independent manner. We show clinical evidence that expression of MAST1, both initial and cisplatin-induced, contributes to platinum resistance and worse clinical outcome. Targeting MAST1 with lestaurtinib, a recently identified MAST1 inhibitor, restores cisplatin sensitivity, leading to the synergistic attenuation of cancer cell proliferation and tumor growth in human cancer cells and patient-derived xenograft models.
Pubmed ID: 30033091 RIS Download
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This monoclonal targets Ki67 antibody [EPR3610]
View all literature mentionsThis polyclonal targets Phospho-B-Raf (Ser445)
View all literature mentionsThis monoclonal targets Jak2 (D2E12) XP Rabbit mAb
View all literature mentionsThis polyclonal targets Flt-3/Flk-2 (C-20)
View all literature mentionsThis monoclonal targets Histone H3
View all literature mentionsThis monoclonal targets FANCL
View all literature mentionsThis monoclonal targets FANCF (D-2)
View all literature mentionsThis polyclonal targets FANCI antibody
View all literature mentionsThis polyclonal targets FANCE
View all literature mentionsThis polyclonal targets Chk2, phospho (Thr68)
View all literature mentionsThis monoclonal targets Chek1
View all literature mentionsThis monoclonal targets Chk1, phospho (Ser345)
View all literature mentionsThis monoclonal targets ATM (D2E2) Rabbit mAb
View all literature mentionsThis monoclonal targets ATM, phospho (Ser1981)
View all literature mentionsThis polyclonal targets ATR (phospho Thr1989)
View all literature mentionsThis polyclonal targets FANCD2
View all literature mentionsThis monoclonal targets Akt1
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets p-Stat3
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Cisplatin modified DNA antibody [CP9/19]
View all literature mentionsThis unknown targets 53BP1, phospho (Ser1778)
View all literature mentionsThis monoclonal targets Histone H2A.X, phospho (Ser139)
View all literature mentionsThis monoclonal targets Bad (D24A9) Rabbit mAb
View all literature mentionsThis monoclonal targets Bad, phospho (Ser112)
View all literature mentionsThis monoclonal targets Bcl-xL (H-5)
View all literature mentionsThis monoclonal targets Human MCL1
View all literature mentionsThis monoclonal targets Human BID
View all literature mentionsThis polyclonal targets Bcl-2 (Human Specific)
View all literature mentionsThis monoclonal targets Cleaved PARP (Asp214)
View all literature mentionsThis monoclonal targets Bim (C34C5) Rabbit mAb
View all literature mentionsThis monoclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis monoclonal targets c-Raf-1
View all literature mentionsThis polyclonal targets c-Raf
View all literature mentionsThis monoclonal targets MEK1
View all literature mentionsThis monoclonal targets Phospho-MEK1/2 (Ser221) (166F8) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-MEK1/2 (Ser217/221)
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis monoclonal targets Glutathione-S-Transferase (GST) antibody produced in mouse
View all literature mentionsThis monoclonal targets MBP (F-6)
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsCell line NCI-H358 is a Cancer cell line with a species of origin Homo sapiens (Human)
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
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View all literature mentionsCell line MV4-11 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line OVCAR-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SK-OV-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SW626 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DMS 153 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DMS 114 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DMS 53 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H526 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H209 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H187 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H146 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H128 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H157 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1975 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H460 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1299 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line KB-3-1 is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line SqCC/Y1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line PCI-13 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-1483 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line JHU-022 is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line UM-SCC-22B is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line FaDu is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Tu 167 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line UM-SCC-47 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line UD-SCC-2 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Tu 212LN is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line PCI-15A is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line UM-SCC-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line PCI-37B is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Tu 212 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-686Tu is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A2780-1A9 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line BG1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H358 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H358 is a Cancer cell line with a species of origin Homo sapiens (Human)
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg