Proline-rich tyrosine kinase 2 and its phosphorylated form pY881 are novel prognostic markers for non-small-cell lung cancer progression and patients’ overall survival

Kuang, Bo-Hua; Zhang, M. Q.; Xu, Li; Hu, Li; Wang, H. B.; Zhao, Weifeng; Du, Yong; Zhang, Xing

doi:10.1038/bjc.2013.439

Cited by 34 publications

(30 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aberrant upregulation of Pyk2 has been shown to correlate with poor prognosis in lung cancer and facilitate epithelial-to-mesenchymal transition in breast cancer. 17,18 Nevertheless, the putative oncogenic role of Pyk2 in cancers in general and in specific hematologic malignancies has not been previously described.…”

Section: Introductionmentioning

confidence: 99%

Pyk2 promotes tumor progression in multiple myeloma

Zhang

Moschetta

Huynh

et al. 2014

Blood

View full text Add to dashboard Cite

• Pyk2 plays a tumor-promoting role in MM progression via modulation of the Wnt/ b-catenin signaling pathway.• Pyk2 inhibitors represent a new therapeutic option against MM.Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family that has been recently linked to tumor development. However, its role in modulating multiple myeloma (MM) biology and disease progression remains unexplored. We first demonstrated that patients with MM present with higher expression of Pyk2 compared with healthy individuals. By using loss-of-function approaches, we found that Pyk2 inhibition led to reduction of MM tumor growth in vivo as well as decreased cell proliferation, cellcycle progression, and adhesion ability in vitro. In turn, overexpression of Pyk2 promoted the malignant phenotype, substantiated by enhanced tumor growth and reduced survival. Mechanistically, inhibition of Pyk2 reduced activation of Wnt/b-catenin signaling by destabilizing b-catenin, leading to downregulation of c-Myc and Cyclin D1. Furthermore, treatment of MM cells with the FAK/Pyk2 inhibitor VS-4718 effectively inhibited MM cell growth both in vitro and in vivo. Collectively, our findings describe the tumor-promoting role of Pyk2 in MM, thus providing molecular evidence for a novel tyrosine kinase inhibitor as a new therapeutic option in MM. (Blood. 2014;124(17):2675-2686

show abstract

Section: Introductionmentioning

confidence: 99%

Pyk2 promotes tumor progression in multiple myeloma

Zhang

Moschetta

Huynh

et al. 2014

Blood

View full text Add to dashboard Cite

show abstract

“…Immunohistochemistry was performed as previously described (27). The relevant, sections were incubated with an anti-TACC3 monoclonal antibody (1:800; Abcam, Cambridge, UK) at 4˚C overnight.…”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as previously described (27). The membrane was incubated with primary antibodies (1:1,000) at 4˚C overnight, followed by incubation with horseradish peroxidase-conjugated goat antimouse or anti-rabbit IgG secondary antibody (1:3,000) (both from Abcam) at room temperature for 1 h. A mouse β-actin monoclonal antibody (1:4,000; Cell Signaling Technology, Danvers, MA, USA) was used as an internal loading control.…”

Section: Methodsmentioning

confidence: 99%

The clinical significance of transforming acidic coiled-coil protein 3 expression in non-small cell lung cancer

et al. 2015

View full text Add to dashboard Cite

Abstract.The relationship between TACC3, a member of the transforming acidic coiled-coil proteins (TACCs) family, and lung carcinoma remains unclear. The present study was designed to explore the prognostic and clinical significance of TACC3 in non-small cell lung cancer (NSCLC). An immunohistochemistry (IHC) assay was performed to analyze the expression of TACC3 in 195 lung cancer cases. The mRNA and protein levels of TACC3 were examined by quantitative reverse transcription-PCR or western blotting. The correlation between TACC3 expression and clinicopathological factors was analyzed by χ 2 analysis and Fisher's exact test. Kaplan-Meier analysis and the Cox proportional hazards model were used to examine the correlation of prognostic outcomes with TACC3. The results showed that the levels of TACC3 mRNA and total protein were higher in lung cancer lesions than paired non-cancerous tissues. IHC analysis revealed that TACC3 was highly expressed in 94 (48.2%) cases. The expression of TACC3 was strongly correlated with smoking status, histological classification, differentiation, cytokeratin 19 fragment levels, T stage and the clinical stage of NSCLC patients. Univariate and multivariate analyses demonstrated that TACC3 is a useful biomarker for NSCLC prognosis. The low TACC3 expression group exhibited better progression-free survival (PFS) among patients who received anti-microtubule chemotherapy. In conclusion, the results showed that a high level of TACC3 expression was correlated with advanced clinicopathological classifications, poor overall survival (OS) and poor recurrence-free survival (RFS) in NSCLC patients.Our findings indicate that TACC3 is a potential prognostic marker and therapeutic target for NSCLC.

show abstract

“…By contrast, the depletion of BMI-1 in certain pancreatic cancer cell lines was found to suppress cell proliferation, sensitize apoptosis and inhibit tumor formation in nude mice (13,(23)(24)(25). In addition, upregulation of BMI-1 expression enhanced the ability of colony formation in a soft agar assay in non-small cell lung cancer (NSCLC) tissues (26).…”

Section: Bmi-1 and Cancermentioning

confidence: 99%

BMI-1, a promising therapeutic target for human cancer

Wang

Cui

et al. 2015

Oncology Letters

View full text Add to dashboard Cite

Abstract. BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types.

show abstract

Proline-rich tyrosine kinase 2 and its phosphorylated form pY881 are novel prognostic markers for non-small-cell lung cancer progression and patients’ overall survival

Cited by 34 publications

References 37 publications

Pyk2 promotes tumor progression in multiple myeloma

Pyk2 promotes tumor progression in multiple myeloma

The clinical significance of transforming acidic coiled-coil protein 3 expression in non-small cell lung cancer

BMI-1, a promising therapeutic target for human cancer

Contact Info

Product

Resources

About