Dataset Information

EGFRwt/vIII-PKM2-?-catenin cascade affects proliferation and chemo-sensitivity in head and neck squamous cell carcinoma.

ABSTRACT: Patients suffered from head and neck squamous cell carcinoma (HNSCC) have an overall poor prognosis owing to proliferation and resistance to treatment. Hence, mining the underlying mechanism of malignancies above and translating the bench outcomes to clinical practice are in urgent need. Previous studies found that the epidermal growth factor receptor (EGFR) increases and co-expresses with EGFRvIII in HNSCC tissues, which indicates poor prognosis of HNSCC patients. Here, we clarify that compared with EGFRwt, EGFRwt/vIII enhances the capability of proliferation and colony formation in HNSCC cells in vitro, and reduces the sensitivity to cisplatin. Furthermore, EGFRwt/vIII induces nuclear translocation of the M2 isoform of pyruvate kinase (PKM2) in a time-dependent manner. The aberrant expression of PKM2 in HNSCC suggests unfavorable outcome. Especially, nuclear PKM2 determines the activation of ?-catenin signaling and regulates the proliferation and chemo-sensitivity of HNSCC cells. Together, our findings demonstrate that EGFRwt/vIII-PKM2-?-catenin cascade controls the proliferation and chemo-sensitivity of HNSCC, thereby providing a promising strategy for diagnosis and therapy of HNSCC.

SUBMITTER: Jing C

PROVIDER: S-EPMC5752689 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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EGFRwt/vIII-PKM2-β-catenin cascade affects proliferation and chemo-sensitivity in head and neck squamous cell carcinoma.

Jing Chao C Qu Xin X Li Zhaoqing Z Wu Chuanqiang C Zhao Minghui M Wang Yu Y Sun Shanshan S Zhang Shengchi S Chen Jinliang J Qiao Yu Y Hu Xiaomeng X Yao Xiaofeng X Jin Rui R Wang Xudong X Zhang Lun L Zhou Xuan X

American journal of cancer research 20171201 12

Patients suffered from head and neck squamous cell carcinoma (HNSCC) have an overall poor prognosis owing to proliferation and resistance to treatment. Hence, mining the underlying mechanism of malignancies above and translating the bench outcomes to clinical practice are in urgent need. Previous studies found that the epidermal growth factor receptor (EGFR) increases and co-expresses with EGFRvIII in HNSCC tissues, which indicates poor prognosis of HNSCC patients. Here, we clarify that compared ...[more]

PMID: 29312802

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Project description:BackgroundTumorigenesis is a complex process of accumulated alteration in function of multiple genes and pathways. Wnt signalling pathway is involved in various differentiation events during embryonic development and is conserved in various species.ObjectiveA multicentre collaborative initiative is undertaken to study the occurrence, prognosis and molecular mechanism of HNSCC (Head and Neck Squamous Cell Carcinoma) which is highly prevalent in eastern parts of India. From a large cohort of HNSCC tissue repository, 67 cases were selected for multi-parametric investigation.Results67 cases showed stable ?-catenin expression. We have seen correlation, if any, of the transcription factor - ?-catenin, telomere maintenance and shelterin complex proteins - TRF2, Rap1 and hTert with respect to tumor differentiation and telomere dysfunction. Immunohistochemistry of ?-catenin protein showed stable and high expression in tumor when compared to stroma. MDSCC (Moderately Differentiated Squamous cell carcinoma) cases expressed nuclear expression of ?-catenin in invasive fronts and showed increased genomic instability. Higher frequency of Anaphase bridges was observed ranging from <3% in normal cut margin to 13% in WDSCC (Well differentiated squamous cell carcinoma) and 18% in MDSCC (Moderately differentiated Squamous cell carcinoma). There was significant decrease in telomere length in MDSCC (<4) when compared to the normal cut margin samples (<7). Quantitative Real Time-PCR confirmed a significant correlationship between stable ?-catenin expression and poor clinical and pathological outcome.ConclusionThe Stabilisation and accumulation of ?-catenin was significant and correlated well with de-differentiation process as well as prognosis and therapy outcome of the patients in the cohort. Expression status of molecular markers such as ?-catenin, hTert, TRF2 and RAP1 correlate significantly with the process of tumorigenesis and prognosis and may play a role in therapeutic management of Head and neck patients.

Dataset Information

EGFRwt/vIII-PKM2-?-catenin cascade affects proliferation and chemo-sensitivity in head and neck squamous cell carcinoma.

Publications

EGFRwt/vIII-PKM2-β-catenin cascade affects proliferation and chemo-sensitivity in head and neck squamous cell carcinoma.

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