Dual c-JunN-terminal kinase-cyclin D1 and extracellular signal-related kinase-c-Jun disjunction in human melanoma

Abstract

Dual disjunction between JNK-cyclin D1 and ERK-c-Jun signalling forms the basis for further investigation of combined JNK and MAPK signalling blockade as a more effective therapeutic approach in human melanoma.

JNK-ERK signalling in melanoma: rewired or entangled?

“…S3 in Pathria et al .) . Therefore, while the pharmacological results appear to contradict, the genetic results support Lopez‐Bergami et al .…”

“…Using two different JNK inhibitors in a panel of melanoma cell lines they show that JNK signalling is required for proliferation and survival of melanoma, independent of the mutational status . Pharmacological JNK inhibition mitigated c‐JUN activity and expression but failed to suppress cyclin D1 levels both at the protein and transcript levels and, consequently, to induce G 1 arrest . However, silencing c‐JUN by small interfering RNA (siRNA) decreased cyclin D1 levels (see Supplementary Fig.…”

“…In this issue of the British Journal of Dermatology , Pathria and colleagues challenge this idea, as they report a dual disjunction of JNK–cyclin D1 and ERK–c‐JUN in melanoma . Using two different JNK inhibitors in a panel of melanoma cell lines they show that JNK signalling is required for proliferation and survival of melanoma, independent of the mutational status .…”

“…In this issue of the British Journal of Dermatology , Pathria and colleagues challenge this idea, as they report a dual disjunction of JNK–cyclin D1 and ERK–c‐JUN in melanoma . Using two different JNK inhibitors in a panel of melanoma cell lines they show that JNK signalling is required for proliferation and survival of melanoma, independent of the mutational status . Pharmacological JNK inhibition mitigated c‐JUN activity and expression but failed to suppress cyclin D1 levels both at the protein and transcript levels and, consequently, to induce G 1 arrest .…”

How breakthroughs in translational research have impacted treatment strategies for melanoma

“…Recently, the c‐Jun N ‐terminal kinase (JNK) signalling cascade, which is important for tumour cell proliferation, has been implicated in resistance of melanoma to MAPK inhibition. Building upon this finding, a study by Pathria et al demonstrated that combination treatment of BRAF mutant melanoma with MAPK kinase (MEK) and JNK inhibitors significantly inhibited proliferation compared with single‐agent treatment, indicating that targeting of multiple prosurvival signalling pathways may be necessary to overcome acquired resistance to BRAF/MEK inhibition …”