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Kallikrein-related peptidases 4, 5, 6 and 7 regulate tumour-associated factors in serous ovarian cancer

Published on Oct 1, 2018in British Journal of Cancer5.42
· DOI :10.1038/s41416-018-0260-1
Ping Wang1
Estimated H-index: 1
(TUM: Technische Universität München),
Viktor Magdolen38
Estimated H-index: 38
(TUM: Technische Universität München)
+ 9 AuthorsDaniela Loessner19
Estimated H-index: 19
(QUT: Queensland University of Technology)
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Abstract
Tissue kallikrein-related peptidases 4, 5, 6 and 7 (KLK4–7) strongly increase the malignancy of ovarian cancer cells. Deciphering their downstream effectors, we aimed at finding new potential prognostic biomarkers and treatment targets for ovarian cancer patients. KLK4–7-transfected (OV-KLK4–7) and vector-control OV-MZ-6 (OV-VC) ovarian cancer cells were established to select differentially regulated factors. With three independent approaches, PCR arrays, genome-wide microarray and proteome analyses, we identified 10 candidates (MSN, KRT19, COL5A2, COL1A2, BMP5, F10, KRT7, JUNB, BMP4, MMP1). To determine differential protein expression, we performed western blot analyses, immunofluorescence and immunohistochemistry for four candidates (MSN, KRT19, KRT7, JUNB) in cells, tumour xenograft and patient-derived tissues. We demonstrated that KLK4–7 clearly regulates expression of MSN, KRT19, KRT7 and JUNB at the mRNA and protein levels in ovarian cancer cells and tissues. Protein expression of the top-upregulated effectors, MSN and KRT19, was investigated by immunohistochemistry in patients afflicted with serous ovarian cancer and related to KLK4–7 immunoexpression. Significant positive associations were found for KRT19/KLK4, KRT19/KLK5 and MSN/KLK7. These findings imply that KLK4–7 exert key modulatory effects on other cancer-related genes and proteins in ovarian cancer. These downstream effectors of KLK4–7, MSN and KRT19 may represent important therapeutic targets in serous ovarian cancer.
  • References (53)
  • Citations (2)
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References53
Newest
Published on Jan 4, 2018in CA: A Cancer Journal for Clinicians223.68
Rebecca L. Siegel43
Estimated H-index: 43
(ACS: American Cancer Society),
Kimberly D. Miller Mph2
Estimated H-index: 2
(ACS: American Cancer Society),
Ahmedin Jemal Dvm3
Estimated H-index: 3
(ACS: American Cancer Society)
Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the Nation...
Published on Jan 1, 2018in CA: A Cancer Journal for Clinicians223.68
Rebecca L. Siegel43
Estimated H-index: 43
,
Kimberly D. Miller16
Estimated H-index: 16
,
Ahmedin Jemal100
Estimated H-index: 100
Published on Nov 1, 2017in Cancer Medicine3.36
Takayuki Kawai12
Estimated H-index: 12
(Kyoto University),
Kentaro Yasuchika3
Estimated H-index: 3
(Kyoto University)
+ 13 AuthorsRyoya Yamaoka5
Estimated H-index: 5
(Kyoto University)
The current lack of an easily measurable surrogate marker of cancer stem cells (CSCs) prevents the clinical application of CSCs for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker associated with transforming growth factor beta (TGFβ)/Smad signaling, and that K19+ HCC-CSCs could be a new therapeutic target of TGFβ receptor 1 inhibitor LY2157299. In this study, we examined whether K19+ HCC-CSCs can be tracked using cytokeratin 19 fragment CYF...
Published on Jan 26, 2017in Biological Chemistry3.01
Michaela Aubele29
Estimated H-index: 29
,
Axel Walch52
Estimated H-index: 52
+ 9 AuthorsC.G.J. Sweep3
Estimated H-index: 3
Triple-negative breast cancer (TNBC), lacking the steroid hormone receptors ER and PR and the oncoprotein HER2, is characterized by its aggressive pattern and insensitivity to endocrine and HER2-directed therapy. Human kallikrein-related peptidases KLK1-15 provide a rich source of serine protease-type biomarkers associated with tumor growth and cancer progression for a variety of malignant diseases. In this study, recombinant KLK4 protein was generated and affinity-purified KLK4-directed polyclo...
Published on Jun 1, 2017in Clinical & Experimental Metastasis2.51
Michaela Bartova2
Estimated H-index: 2
,
Juraj Hlavaty10
Estimated H-index: 10
+ 4 AuthorsIngrid Walter26
Estimated H-index: 26
Ezrin, radixin, moesin (ERM) are important membrane-cytoskeletal crosslinkers and are suggested to play important role in cancer progression and metastasis. Even though ERM proteins were generally considered to be functionally redundant and the most studied was ezrin, recent studies highlight their distinct roles in metastatic process. Little information is available regarding the role of individual ERM proteins and their phosphorylated forms in human breast cancer. Our study is the first to exa...
Published on Mar 1, 2017in American Journal of Pathology3.76
Mark Pines42
Estimated H-index: 42
,
Oshrat Levi4
Estimated H-index: 4
+ 4 AuthorsOrna Halevy36
Estimated H-index: 36
(HUJI: Hebrew University of Jerusalem)
Fibrosis is the main complication of muscular dystrophies. We identified moesin, a member of the ezrin-radixin-moesin family, in dystrophic muscles of mice representing Duchenne and congenital muscular dystrophies (DMD and CMD, respectively) and dysferlinopathy, but not in the wild type. High levels of moesin were also observed in muscle biopsy specimens from DMD, Ullrich CMD, and merosin-deficient CMD patients, all of which present high levels of fibrosis. The myofibroblasts, responsible for ex...
Published on Jan 1, 2017in Theranostics8.06
Yuanyuan Qin2
Estimated H-index: 2
,
Weilong Chen3
Estimated H-index: 3
+ 8 AuthorsSuling Liu2
Estimated H-index: 2
Published on Dec 1, 2016in Nature Reviews Immunology44.02
WanJun Chen1
Estimated H-index: 1
,
Peter ten Dijke1
Estimated H-index: 1
In this Review, the authors discuss the emerging roles for members of the transforming growth factor-β (TGFβ) superfamily in regulating immune responses. In particular, they focus on how activin A and bone morphogenetic proteins (BMPs) regulate innate and adaptive immune cells in inflammatory diseases and cancer.
Cited By2
Newest
Published on Dec 1, 2019in BMC Cancer2.93
Weiwei Gong (TUM: Technische Universität München), Yueyang Liu1
Estimated H-index: 1
(TUM: Technische Universität München)
+ 6 AuthorsJulia Dorn14
Estimated H-index: 14
(TUM: Technische Universität München)
Background In ovarian cancer, dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is observed. In this study, we have analyzed the KLK5 mRNA expression pattern in tumor tissue of patients suffering from high-grade serous ovarian cancer stage FIGO III/IV. Moreover, we have correlated the KLK5 mRNA levels with clinical outcome.
Published on Sep 11, 2019in Frontiers in Oncology
Jun Lu3
Estimated H-index: 3
(SJTU: Shanghai Jiao Tong University),
Qin Shi + 8 AuthorsXiaodong Zhao4
Estimated H-index: 4
(SJTU: Shanghai Jiao Tong University)
The oral multi-targeted tyrosine kinase inhibitor (TKI) anlotinib is effective for non-small cell lung cancer (NSCLC) in clinical trials at 3rd line. However, a fraction of patients remains nonresponsive, raising the need of how to identify anlotinib-responsive patients. In the present study, we aimed to screen potential biomarkers for anlotinib-responsive stratification via integrated transcriptome analysis. Comparing with the anlotinib-sensitive lung cancer cell NCI-H1975, we found 1,315 genes...
View next paperAdvanced high-grade serous ovarian cancer: inverse association of KLK13 and KLK14 mRNA levels in tumor tissue and patients’ prognosis