Kallikrein 6 protease advances colon tumorigenesis via induction of the high mobility group A2 protein.

Kallikrein 6 protease advances colon tumorigenesis via induction of the high mobility group A2 protein. Oncotarget. 2019 Oct 22;10(58):6062-6078 Authors: Chen H, Sells E, Pandey R, Abril ER, Hsu CH, Krouse RS, Nagle RB, Pampalakis G, Sotiropoulou G, Ignatenko NA Abstract Kallikrein-related peptidase 6 (KLK6) overexpression is commonly observed in primary tumors of colorectal cancer (CRC) patients and has been associated with tumor aggressiveness, metastasis, and poor prognosis. We previously established a unique contribution of KLK6 in colon cancer metastasis via a specific network of microRNAs and mRNAs. Here we evaluated the cellular functions of KLK6 protease in Caco-2 colon adenocarcinoma cell line after introduction of the enzymatically active or inactive form of the enzyme. We found that proteolytically active KLK6 increased Caco-2 cells invasiveness in vitro and decreased the animal survival in the orthotopic colon cancer model. The active KLK6 induced phosphorylation of SMAD 2/3 proteins leading to the altered expression of the epithelial-mesenchymal transition (EMT) markers. KLK6 overexpression also induced the RNA-binding protein LIN28B and high-mobility group AT-hook 2 (HMGA2) transcription factor, two essential regulators of cell invasion and metastasis. In the CRC patients, KLK6 protein levels were elevated in the non-cancerous distant and adjacent tissues, compared to their paired tumor tissues (p < 0.0001 and p = 0....
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research