Klk14, a serine protease, is linked to multiple pathologies. It belongs to the kallikrein-related peptidases family and is involved in the HGF/Met signaling pathway. By proteolytically inhibiting HGF activator-inhibitor 1 (HAI-1), which strongly inhibits pro-HGF activators, KLK14 contributes to tumor progression [1]. In the epidermis, imbalance in proteolytic activity due to deficiency of LEKTI leads to increased activities of KLK14 among others, resulting in Netherton syndrome [2].

In prostate cancer, KLK14 protein expression correlates with pathological tumor status and disease progression as defined by prostate-specific antigen relapse, making it an independent prognostic factor [4]. In breast cancer, KLK14 is overexpressed compared to normal breast tissues and is associated with higher tumor grade and positive nodal status [5]. Also, in salivary gland tumors, KLK14 shows differential expression among different tumor types, suggesting its potential as a biomarker [3].

In conclusion, Klk14 is a significant protease involved in multiple disease conditions, especially cancers. Its role in disease progression and potential as a biomarker, as revealed through various studies, underscores the importance of further functional studies, which could potentially be facilitated by gene knockout (KO) or conditional knockout (CKO) mouse models to better understand its functions and develop targeted therapies for related diseases.

References:

1. Solís-Calero, Christian, Carvalho, Hernandes F. 2017. KLK14 interactions with HAI-1 and HAI-2 serine protease inhibitors: A molecular dynamics and relative free-energy calculations study. In Cell biology international, 41, 1246-1264. doi:10.1002/cbin.10839. https://pubmed.ncbi.nlm.nih.gov/28817220/

2. Chavarria-Smith, Joseph, Chiu, Cecilia P C, Jackman, Janet K, Koerber, James T, Yi, Tangsheng. 2022. Dual antibody inhibition of KLK5 and KLK7 for Netherton syndrome and atopic dermatitis. In Science translational medicine, 14, eabp9159. doi:10.1126/scitranslmed.abp9159. https://pubmed.ncbi.nlm.nih.gov/36516271/

3. Hashem, Nelly N, Mara, Thomas W, Mohamed, Mohamed, Diamandis, Eleftherios P, Darling, Mark R. . Human kallikrein 14 (KLK14) expression in salivary gland tumors. In The International journal of biological markers, 25, 32-7. doi:. https://pubmed.ncbi.nlm.nih.gov/20155713/

4. Rabien, Anja, Fritzsche, Florian, Jung, Monika, Stephan, Carsten, Kristiansen, Glen. 2008. High expression of KLK14 in prostatic adenocarcinoma is associated with elevated risk of prostate-specific antigen relapse. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 29, 1-8. doi:10.1159/000132565. https://pubmed.ncbi.nlm.nih.gov/18497543/

5. Fritzsche, F, Gansukh, T, Borgoño, C A, Dahl, E, Kristiansen, G. . Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with higher tumour grades and positive nodal status. In British journal of cancer, 94, 540-7. doi:. https://pubmed.ncbi.nlm.nih.gov/16434994/