KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

Koistinen, Hannu; Künnapuu, Jaana; Jeltsch, Michael

doi:10.3390/ijms222413545

Cited by 8 publications

(18 citation statements)

References 119 publications

(162 reference statements)

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“…Serum PSA level aids in the detection and follow-up of prostatic cancer. KLK3 gene alternative splicing results in many transcript variants that each encode a different isoform [12].…”

Section: Discussionmentioning

confidence: 99%

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Association of Kallikrein Related Peptidase 3 (KLK3) Gene with Dermatophytosis in the UK Biobank cohort

Lehrer

Rheinstein²

2022

Preprint

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In a previous genome wide association study (GWAS) of UK Biobank (UKB) data, we identified one susceptibility locus, Tubulointerstitial Nephritis Antigen (TINAG), with genome wide significance for dermatophytosis. We used genotype calls from file UKB22418. These data are derived directly from Affymetrix DNA microarrays but are missing many genotype calls. Using computationally efficient approaches, UKB has entered imputed genotypes into a second dataset, UKB22828, increasing the number of testable variants by over 100-fold to 96 million variants. In the current study, we used UKB imputed genotypes in UKB22828 to identify dermatophytosis susceptibility loci. Methods: To identify cases of dermatophytosis, we used ICD10 code B35, which covers Tinea barbae, Tinea capitis, Tinea unguium, Tinea manuum, Tinea pedis, Tinea corporis, Tinea imbricata, Tinea cruris, other dermatophytoses, and dermatophytosis, unspecified. We used PLINK, a whole-genome association analysis toolset, to analyze the UKB22828 chromosome files. Results: GWAS summary (Manhattan) plot of the meta-analysis association statistics highlighted two susceptibility loci, TINAG and Kallikrein Related Peptidase 3 (KLK3), with genome wide significance for dermatophytosis. Conclusion: KLK3 may be a dermatophytosis susceptibility gene. KLK3 could affect risk of dermatophytosis, since kallikreins are necessary for normal homeostasis of the skin.

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“…Serum PSA level aids in the detection and follow-up of prostatic cancer. KLK3 gene alternative splicing results in many transcript variants that each encode a different isoform [12].…”

Section: Discussionmentioning

confidence: 99%

“…Serum PSA level aids in the detection and follow-up of prostatic cancer. KLK3 gene alternative splicing results in many transcript variants that each encode a different isoform [12]. KLK3 could affect risk of dermatophytosis, since kallikreins are necessary for normal homeostasis of the skin.…”

Section: Discussionmentioning

confidence: 99%

Association of Kallikrein Related Peptidase 3 (KLK3) Gene with Dermatophytosis in the UK Biobank cohort

Lehrer

Rheinstein²

2022

Preprint

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“…9,[54][55][56][57] The physiological function of KLK3, and probably also of other major prostatic KLKs, is to promote sperm motility by cleaving semenogelins, thereby dissolving the seminal clot formed after ejaculation. 71 Several KLKs have also been suggested to promote or inhibit tumor growth and metastasis 9,[54][55][56][57]72,73 (Figure 1). These functions may be mediated via proteolytic cascades 74,75 or directly, for example, by activation of protease-activated receptors (PARs), which are G-protein coupled receptors, or other cell surface or secreted proteins.…”

Section: Proteases In Prostate Cancermentioning

confidence: 99%

“…85,86 As tumors need to establish blood circulation in order to grow beyond microscopic size, the slow growth of many prostate cancers has been proposed to be dependent on this antiangiogenic activity of KLK3. 54,73,84 However, KLK3 was recently found to activate vascular endothelial growth factor-C (VEGF-C) and VEGF-D, which may support angiogenesis and tumor growth. 73,77 These observations are not necessarily in conflict, since KLK3-activated VEGF-C is lymphangiogenic rather than angiogenic, and the overall effect of KLK3 is likely dependent on several different factors, including expression of different VEGFs and other (anti)angiogenic factors, along with their activating proteases.…”

Section: Proteases In Prostate Cancermentioning

confidence: 99%

The roles of proteases in prostate cancer

et al. 2023

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Since the proposition of the pro‐invasive activity of proteolytic enzymes over 70 years ago, several roles for proteases in cancer progression have been established. About half of the 473 active human proteases are expressed in the prostate and many of the most well‐characterized members of this enzyme family are regulated by androgens, hormones essential for development of prostate cancer. Most notably, several kallikrein‐related peptidases, including KLK3 (prostate‐specific antigen, PSA), the most well‐known prostate cancer marker, and type II transmembrane serine proteases, such as TMPRSS2 and matriptase, have been extensively studied and found to promote prostate cancer progression. Recent findings also suggest a critical role for proteases in the development of advanced and aggressive castration‐resistant prostate cancer (CRPC). Perhaps the most intriguing evidence for this role comes from studies showing that the protease‐activated transmembrane proteins, Notch and CDCP1, are associated with the development of CRPC. Here, we review the roles of proteases in prostate cancer, with a special focus on their regulation by androgens.

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“…Proteases are excellent biomarkers in PCa as about half of the human proteases are expressed in the prostate gland [ 100 ]. KLK3 , encoding PSA, is one of the members of the kallikrein-related peptidase family, and it is highly expressed in the prostate [ 101 ]. In addition to its widespread role in PCa diagnosis, KLK3 is involved in the progression of tumors towards metastasis by supporting cell proliferation and angiogenesis [ 102 ].…”

Section: Tissue Prostate Cancer Biomarkersmentioning

confidence: 99%

Biomarkers for the Detection and Risk Stratification of Aggressive Prostate Cancer

Eickelschulte

Riediger

Angeles

et al. 2022

Cancers

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Current strategies for the clinical management of prostate cancer are inadequate for a precise risk stratification between indolent and aggressive tumors. Recently developed tissue-based molecular biomarkers have refined the risk assessment of the disease. The characterization of tissue biopsy components and subsequent identification of relevant tissue-based molecular alterations have the potential to improve the clinical decision making and patient outcomes. However, tissue biopsies are invasive and spatially restricted due to tumor heterogeneity. Therefore, there is an urgent need for complementary diagnostic and prognostic options. Liquid biopsy approaches are minimally invasive with potential utility for the early detection, risk stratification, and monitoring of tumors. In this review, we focus on tissue and liquid biopsy biomarkers for early diagnosis and risk stratification of prostate cancer, including modifications on the genomic, epigenomic, transcriptomic, and proteomic levels. High-risk molecular alterations combined with orthogonal clinical parameters can improve the identification of aggressive tumors and increase patient survival.

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KLK3 in the Regulation of Angiogenesis—Tumorigenic or Not?

Cited by 8 publications

References 119 publications

Association of Kallikrein Related Peptidase 3 (KLK3) Gene with Dermatophytosis in the UK Biobank cohort

Association of Kallikrein Related Peptidase 3 (KLK3) Gene with Dermatophytosis in the UK Biobank cohort

The roles of proteases in prostate cancer

Biomarkers for the Detection and Risk Stratification of Aggressive Prostate Cancer

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