Upregulation of pAKT(Ser473) expression in progression of HPV‐positive oropharyngeal squamous cell carcinoma

Horn, Dominik; Freudlsperger, Christian; Holzinger, Dana; Kunzmann, Kevin; Plinkert, Peter K.; Dyckhoff, Gerhard; Hoffmann, Jürgen; Freier, Kolja; Heß, Jochen

doi:10.1002/hed.24910

Cited by 15 publications

(10 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PI3k/AKT pathway is one of the major signaling cascades overactivated in various tumor entities including OPSCC [29]. To gain insight into the correlation of PI3k/AKT and MEK1-ERK1/2 pathway in OPSCC, pERK1/2 staining patterns were compared with data for pAKT (Ser473) phosphorylation, which were assessed previously [25]. IRS data for both pERK1/2 and pAKT (Ser473) were available for 109 cases of our OPSCC cohort.…”

Section: Resultsmentioning

confidence: 99%

“…HPV-positive oropharyngeal SCC showed activating mutations of PIK3CA in 56% [24]. In a recent study, we found pAKT (Ser473) expression serves as an independent prognostic marker for progression-free survival in OPSCC [25]. So far, only inhibitors of the epidermal growth factor receptor (EGFR) upstream of MAPK/ERK signaling have gained approval for HNSCC treatment [26].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Differential Activation of ERK Signaling in HPV-Related Oropharyngeal Squamous Cell Carcinoma

Chen

Müller

Flechtenmacher

et al. 2019

Cancers

Self Cite

View full text Add to dashboard Cite

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) forms a distinct tumor entity with better survival clinical outcome. Numerous underlying molecular mechanisms have been postulated for differences in treatment response, but the impact of MEK/ERK signaling, a main driver of carcinogenesis in various cancers including OPSCC and key player mediating therapy resistance remains elusive. In a retrospective experimental cohort study, primary tumor samples from OPSCC patients (n = 124) were available on tissue microarrays (TMAs) and expression levels of phosphorylated ERK1/2 (pERK1/2) were detected by immunohistochemical staining. Correlations of pERK1/2 expression patterns with clinicopathological features and clinical outcome were evaluated by statistical analysis. A low pERK1/2 expression was strongly associated with HPV-related OPSCC, while primary tumors with high pERK1/2 staining showed a distinctly worse survival outcome and were associated with higher cellular differentiation. Co-activation of both ERK1/2 and AKT was a common event and was associated with unfavorable prognosis in our cohort. However, the combinatorial analysis of pAKT (Ser473) and pERK1/2 did not strengthen the predictive power of pERK1/2, suggesting that pERK1/2 plays a more significant function in OPSCC. In summary, our data provide a compelling experimental and statistical evidence that low levels of tumor cell intrinsic ERK1/2 activation contribute at least in part to the favorable outcome of HPV-related OPSCC. On the other hand, presented findings indicate that non-HPV-related OPSCC with elevated ERK phosphorylation are at high risk for treatment failure and might benefit from targeted therapy of MEK/ERK signaling.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Differential Activation of ERK Signaling in HPV-Related Oropharyngeal Squamous Cell Carcinoma

Chen

Müller

Flechtenmacher

et al. 2019

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Notably, pAKT (Ser473) expression increased in primary tumors to progressive nodal disease (21.1%; P < 0.011; ref. 25).…”

Section: Akt As a Target In Cancer Therapymentioning

confidence: 99%

AKT as a Therapeutic Target for Cancer

et al. 2019

View full text Add to dashboard Cite

Many cellular processes in cancer are attributed to kinase signaling networks. V-akt murine thymoma viral oncogene homolog (AKT) plays a major role in the PI3K/AKT signaling pathways. AKT is activated by PI3K or phosphoinositidedependent kinases (PDK) as well as growth factors, inflammation, and DNA damage. Signal transduction occurs through downstream effectors such as mTOR, glycogen synthase kinase 3 beta (GSK3b), or forkhead box protein O1 (FOXO1). The abnormal overexpression or activation of AKT has been observed in many cancers, including ovarian, lung, and pancreatic cancers, and is associated with increased cancer cell proliferation and survival. Therefore, targeting AKT could provide an important approach for cancer prevention and therapy. In this review, we discuss the rationale for targeting AKT and also provide details regarding synthetic and natural AKT-targeting compounds and their associated studies.

show abstract

“…[25][26][27][28][29] The score for each individual ranged from 1 to 16 and was calculated by multiplication of score A and B. Secondary antibody detection was performed using the DAKO Real Kit (DAKO, Hamburg, Germany) according to the manufacturer's protocol.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The established scoring system was applied as previously described. [25][26][27][28][29] The score for each individual ranged from 1 to 16 and was calculated by multiplication of score A and B. Scores from 0 to 8 were combined in the CTTN low group.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Cortactin expression: Association with disease progression and survival in oral squamous cell carcinoma

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background Cortactin (CTTN) is located on chromosome 11q13 and is associated with invasiveness in various cancer entities. CTTN protein expression could be a prognosticator of oral squamous cell carcinoma (OSCC) in terms of recurrence and survival. Methods CTTN‐dependent invasion was performed using migration assay in human papillomavirus‐negative head and neck squamous cell carcinoma (HNSCC) cells. Cortactin protein analysis in tissue microarrays was used for correlation with clinical parameters, as well as for survival analysis. Gene expression profiling in HNSCC cells was performed to unreveal CTTN signaling. Results Knockdown of CTTN in HNSCC cells showed less invasion in vitro. Gene expression profiling showed various deregulated genes known to be involved in progression. We confirmed the link between CTTN overexpression and progression in a large clinical cohort. High expression was associated with worse overall and progression‐free survival. Conclusions We propose CTTN for managing OSCC in terms of adjuvant therapy and aftercare. Furthermore, our study reveals new potential targets in CTTN signaling for individualized OSCC therapy.

show abstract

Upregulation of pAKT(Ser473) expression in progression of HPV‐positive oropharyngeal squamous cell carcinoma

Cited by 15 publications

References 45 publications

Differential Activation of ERK Signaling in HPV-Related Oropharyngeal Squamous Cell Carcinoma

Differential Activation of ERK Signaling in HPV-Related Oropharyngeal Squamous Cell Carcinoma

AKT as a Therapeutic Target for Cancer

Cortactin expression: Association with disease progression and survival in oral squamous cell carcinoma

Contact Info

Product

Resources

About