Tyrosine kinase expression profile in clear cell renal cell carcinoma

Behbahani, Turang E; Thierse, Claudia; Baumann, Claudia; Holl, Daniel; Bastian, Patrick J.; Ruecker, Alexander von; Müller, Stefan; Ellinger, Jörg; Hauser, Stefan

doi:10.1007/s00345-011-0767-z

Cited by 42 publications

(27 citation statements)

References 25 publications

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“…Thus, we propose that PTK7 IHC staining grade could be used as a prospective prognostic determinant of ESCC. Although previous studies have reported a decrease in PTK7 expression levels in metastatic melanoma (25) and clear cell renal cell carcinoma, (26) PTK7 has been shown to be upregulated in many types of human malignancy, including colon cancer, lung carcinoma, liposarcoma, gastric cancer, and acute myeloid leukemia. (11,(17)(18)(19)(20)22) Prebet et al (20) reported that increased expression of PTK7 is correlated with poor clinical outcome in acute myeloid leukemia, a finding that was linked to increased cell migration and resistance to apoptosis.…”

Section: Discussionmentioning

confidence: 95%

“…(24) However, PTK7 expression has been shown to be decreased in metastatic melanoma (25) and clear cell renal cell carcinoma. (26) In addition, chromosome 6p, (27) on which the PTK7 gene is located, was found to be deleted in breast carcinoma (28) and malignant melanoma. (29) Although the role of PTK7 in different cancers has not been studied comprehensively, PTK7 is likely to have a tumorpromoting role in general.…”

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confidence: 99%

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Oncogenic role of protein tyrosine kinase 7 in esophageal squamous cell carcinoma

et al. 2013

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Esophageal squamous cell carcinoma (ESCC) is a common subtype of esophageal cancer that is particularly prevalent in East Asian countries. Our previous expression profile analysis showed that the gene encoding protein tyrosine kinase 7 (PTK7) is upregulated in ESCC tissues. Here, we aimed to validate PTK7 as a prognostic factor and a candidate target for molecular treatment of ESCC. Both RT-PCR and Western blot analysis of tissues from ESCC patients revealed that PTK7 was significantly upregulated in tumor tissue samples of ESCC. Immunohistochemical staining of PTK7 showed that increased expression of PTK7 was inversely correlated with overall survival (P = 0.021). In vitro knockdown of PTK7 inhibited proliferation, survival, wound healing, and invasion of ESCC cells. In addition, PTK7 knockdown decreased phosphorylation of Akt, Erk, and focal adhesion kinase (FAK), important determinants of cell proliferation, survival, and migration. Therefore, our findings suggest that PTK7 has potential as a prognostic marker for ESCC and might also be a candidate for targeted therapy in the treatment of ESCC. (Cancer Sci 2013; 104: 1120-1126 E sophageal cancer is one of the most devastating malignancies. Despite recent developments in its management, advanced esophageal cancer is associated with high rates of local recurrence and distant metastasis.(1,2) Although there has been improvement in clinical outcome through multidisciplinary treatment strategies, (3)(4)(5) such as total mediastinal lymph node dissection, (6) and new diagnostic modalities such as positron emission tomography, (7) these developments have not proven satisfactory in preventing the high recurrence rates. Currently, the prognosis is only promising if the tumor is detected early and resected completely.Esophageal squamous cell carcinoma (ESCC) is the most common histologic subtype of esophageal cancer in East Asian countries.(8) It has a unique profile of clinical and anatomical characteristics that is distinct from those of esophageal adenocarcinoma, which is more prevalent in North America, UK, and Australia.(8) To develop prognostic diagnosis and effective therapeutics for ESCC, the identification of biomarkers is of vital importance. In a gene expression profiling analysis to pursue biomarkers, we identified protein tyrosine kinase 7 (PTK7; also known as colon carcinoma kinase-4 or CCK-4), as a candidate biomarker for ESCC. (9) Protein tyrosine kinase 7 is a receptor tyrosine kinase-like molecule containing an extracellular domain with seven immunoglobulin-like loops, a transmembrane domain, and a defective tyrosine kinase domain that resembles a catalytic domain but lacks catalytic activity.(10-12) Mice expressing a truncated form of PTK7 protein die perinatally, revealing a defect in neural tube closure and stereociliary bundle orientation. These findings implicate PTK7 as a regulator of planar cell polarity (PCP).(13) It has been shown that PTK7 recruits RACK1, which affects Dsh recruitment by interaction with PKCd1. (14) Interaction between PTK7...

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Section: Discussionmentioning

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Oncogenic role of protein tyrosine kinase 7 in esophageal squamous cell carcinoma

et al. 2013

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“…In recent years, activation of ABL1 and ABL2 has been detected in solid tumors, including breast, colon, lung, and kidney carcinoma, as well as melanoma 7-16 . Activation of ABL kinases in solid tumors is not linked to chromosome translocation events, but rather is driven by enhanced ABL1 or ABL2 expression and/or by oncogenic tyrosine kinases, chemokine receptors, oxidative stress, and/or inactivation of negative regulatory proteins (cbioportal.org; 3, 16-21 ). Here we compare the modes of ABL family kinase activation in leukemias and solid tumors.…”

Section: Introductionmentioning

confidence: 99%

Role of ABL family kinases in cancer: from leukaemia to solid tumours

et al. 2013

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The Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, transduces diverse extracellular signals to protein networks that control proliferation, survival, migration, and invasion. ABL1 was first identified as an oncogene required for the development of leukemias initiated by retroviruses or chromosome translocations. The demonstration that small molecule ABL kinase inhibitors effectively treat chronic myeloid leukemia opened the door to the era of targeted cancer therapies. Recent reports have uncovered roles for ABL kinases in solid tumors. Enhanced ABL expression and activation in some solid tumors, together with altered cell polarity, invasion or growth induced by activated ABL kinases, suggest that drugs targeting these kinases may have utility in treating selected solid tumors.

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“…Other members of this signaling network have been characterized to play a pro-inflammatory role in ccRCC. These include SCD1 (stearoyl-CoA desaturase 1) [24], BTK (bruton agammaglobulinemia tyrosine kinase) [25, 26], and FXYD5 (FXYD domain containing ion transport regulator 5, dysadherin) [27-29]. CDH13 appears to be frequently methylated in cancer, however its expression has been reported to be upregulated in tumor-associated vasculature, where it promotes endothelial cell proliferation and migration [30].…”

Section: Resultsmentioning

confidence: 99%

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

et al. 2014

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Currently there is a lack of targeted therapies that lead to long-term attenuation or regression of disease in patients with advanced clear cell renal cell carcinoma (ccRCC). Our group has implemented a high-throughput genetic analysis coupled with a high-throughput proliferative screen in order to investigate the genetic contributions of a large cohort of overexpressed genes at the functional level in an effort to better understand factors involved in tumor initiation and progression.Patient gene array analysis identified transcripts that are consistently elevated in patient ccRCC as compared to matched normal renal tissues. This was followed by a high-throughput lentivirus screen, independently targeting 195 overexpressed transcripts identified in the gene array in four ccRCC cell lines. This revealed 31 ‘hits’ that contribute to ccRCC cell proliferation.Many of the hits identified are not only presented in the context of ccRCC for the first time, but several have not been previously linked to cancer. We further characterize the function of a group of hits in tumor cell invasion. Taken together these findings reveal pathways that may be critical in ccRCC tumorigenicity, and identifies novel candidate factors that could serve as targets for therapeutic intervention or diagnostic/prognostic biomarkers for patients with advanced ccRCC.

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Tyrosine kinase expression profile in clear cell renal cell carcinoma

Abstract: TK constitute valuable targets for pharmaceutical anti-cancer therapy. ERBB4 and HCK depict significantly lower expression levels in renal cancer tissues.

Cited by 42 publications

References 25 publications

Oncogenic role of protein tyrosine kinase 7 in esophageal squamous cell carcinoma

Oncogenic role of protein tyrosine kinase 7 in esophageal squamous cell carcinoma

Role of ABL family kinases in cancer: from leukaemia to solid tumours

Functional genomics identifies novel genes essential for clear cell renal cell carcinoma tumor cell proliferation and migration

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