MAPKs activation in head and neck squamous cell carcinomas

Maggioni, Davide; Gaini, Renato Maria; Nicolini, Gabriella; Tredici, G; Garavello, Werner

doi:10.1007/s12156-011-0086-z

Cited by 5 publications

(6 citation statements)

References 65 publications

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“…In particular, ERK is a member of an oncogenic pathway activated by the upstream oncoproteins Ras and Raf (24,40). Upon activation, Erk1/2 phosphorylates either cytoplasmic downstream targets, including p90 ribosomal S6 kinase, or nuclear substrates (24,41).…”

Section: Discussionmentioning

confidence: 99%

“…Mitogen-activated protein kinase (MAPK) pathways are evolutionarily conserved kinase modules that link extracellular signals to the machinery that controls fundamental cellular processes such as growth, proliferation, differentiation, migration and apoptosis (24). MAPKs phosphorylate serine and threonine residues of specific target proteins (25).…”

Section: Erk1/2 Activation and Modulation Of Stat3 Signaling In Oral mentioning

confidence: 99%

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Erk1/2 activation and modulation of STAT3 signaling in oral cancer

et al. 2014

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Abstract. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway possesses confirmed oncogenic potential in oral squamous cell carcinoma (OSCC). Crosstalk with other molecular pathways contributes to STAT3 regulation in cancer. The effects of mitogen-activated protein kinases (MAPKs) and particularly extracellular signal-regulated kinase 1/2 (Erk1/2) on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examined the effects of Erk1/2 modulation on STAT3 signaling and cell growth in OSCC cells. Constitutive expression levels of phosphorylated (tyrosine and serine) and total STAT3, Erk1/2 and cyclin D1 were assessed in OSCC cell lines. Erk1/2 modulation was achieved by pharmacological agents; siRNA silencing against Erk1/2 was also performed. Cell proliferation and viability were assessed. Erk1/2 inhibition with either U0126 treatment or specific siRNA silencing resulted in decreases in p-ser STAT3 and cyclin D1 levels and increases in p-tyr STAT3 in OSCC cells. Moreover, Erk1/2 inhibition resulted in a dose-dependent reduction in OSCC cell growth and viability. Erk1/2 induction had the opposite effects. Taken together, these results are supportive of an active crosstalk between the oncogenic Erk1/2 and STAT3 pathways in OSCC, the significance of which requires further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Erk1/2 Activation and Modulation Of Stat3 Signaling In Oral mentioning

confidence: 99%

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

et al. 2014

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“…The family of mitogen-activated protein kinases (MAPK) are a family of serin-threonin kinases implicated in the regulation of the majority of physiological cellular processes, including proliferation, differentiation, and apoptosis in response to changes in the cellular environment ( 130 ). In particular, the Ras/Raf/MEK/ERK1/2 (extracellular signal-regulated protein kinases) cascade is the MAPK signaling cascade most frequently associated with carcinogenesis of several cancer types ( 131 ).…”

Section: Mechanisms Of Resistance To Cetuximabmentioning

confidence: 99%

Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers

et al. 2021

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most incident cancer worldwide. More than half of HNSCC patients experience locoregional or distant relapse to treatment despite aggressive multimodal therapeutic approaches that include surgical resection, radiation therapy, and adjuvant chemotherapy. Before the arrival of immunotherapy, systemic chemotherapy was previously employed as the standard first-line protocol with an association of cisplatin or carboplatin plus 5-fluorouracil plus cetuximab (anti-EFGR antibody). Unfortunately, acquisition of therapy resistance is common in patients with HNSCC and often results in local and distant failure. Despite our better understanding of HNSCC biology, no other molecular-targeted agent has been approved for HNSCC. In this review, we outline the mechanisms of resistance to the therapeutic strategies currently used in HNSCC, discuss combination treatment strategies to overcome them, and summarize the therapeutic regimens that are presently being evaluated in early- and late-phase clinical trials.

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Section: Jnk1/2 Expression and Modulation Of Stat3 Signaling In Oral mentioning

confidence: 99%

“…MAPKs have been implicated in various cellular processes, including growth, proliferation, differentiation, inflammation and apoptosis (21,22). In HNSCC, MAPKs constitute downstream targets of several molecules, including EGFR, Raf kinase and reactive oxygen species, whose aberrant regulation has been studied in this type of cancer (21,23,24). c-Jun N-terminal kinases (JNKs) are members of the MAPK family, and become activated by a stressful cellular environment, including ultraviolet irradiation, oxidative stress, changes in osmolarity or metabolism, DNA damage, heat shock and inflammatory cytokine signaling (25).…”

Section: Jnk1/2 Expression and Modulation Of Stat3 Signaling In Oral mentioning

confidence: 99%

JNK1/2 expression and modulation of STAT3 signaling in oral cancer

et al. 2016

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Abstract. Mitogen-activated protein kinases (MAPKs) are a family of protein kinases that link extracellular stimuli with intracellular responses and participate in numerous cellular processes such as growth, proliferation, differentiation, inflammation and apoptosis. Persistent activation of signal transducer and activator of transcription 3 (STAT3), which is accompanied by increases in STAT3 tyrosine phosphorylation, is associated with cell proliferation, differentiation and apoptosis in oral squamous cell carcinoma (OSCC). The role and significance of the activation of MAPKs, particularly of c-Jun N-terminal kinase (JNK), on STAT3 signaling in OSCC have not been thoroughly investigated. The present study examines the effects of JNK1/2 modulation on STAT3 signaling and cellular activities in OSCC cells. The expression levels of STAT3 [total, tyrosine phosphorylated (p-Tyr) and serine phosphorylated (p-Ser)], JNK, c-Jun and cyclin D1 were assessed in the OSCC cell lines SCC25 and SCC9. Inhibition of JNK1/2 was achieved by pharmacological agents (SP600125) and by small interfering RNA (siRNA) silencing, while JNK1/2 was induced by active MAPK kinase 7. Cell proliferation and viability rates were also evaluated. Inhibition of JNK1/2 with either SP600125 treatment or specific siRNA silencing resulted in decreased levels of p-Ser STAT3 and increased levels of p-Tyr STAT3 and cyclin D1 in both cell lines. Furthermore, JNK1/2 inhibition resulted in a dose-dependent increase in cell growth and viability in both cell lines. Opposite results were observed with JNK1/2 induction in both cell lines. The present results are supportive of a potential tumor suppressive role of JNK1/2 signaling in OSCC, which may be mediated through negative crosstalk with the oncogenic STAT3 signaling pathway. The possible therapeutic implications of JNK1/2 inhibition for patients with OSCC require to be investigated.

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MAPKs activation in head and neck squamous cell carcinomas

Cited by 5 publications

References 65 publications

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

Erk1/2 activation and modulation of STAT3 signaling in oral cancer

Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers

JNK1/2 expression and modulation of STAT3 signaling in oral cancer

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