The collagen‐modifying enzyme plod2 is induced and required during l1‐mediated colon cancer progression
Cheriyamundath S, Kumar A, Gavert N, Brabletz T, Ben‐ze’ev A (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 22
Article Number: 3552
Journal Issue: 7
DOI: 10.3390/ijms22073552
Abstract
The overactivation of Wnt/β‐catenin signaling is a hallmark of colorectal cancer (CRC) development. We identified the cell adhesion molecule L1CAM (L1) as a target of β‐catenin‐TCF transactivation in CRC cells. The overexpression of L1 in CRC cells confers enhanced proliferation, motility, tumorigenesis and liver metastasis, and L1 is exclusively localized in the invasive areas of human CRC tissue. A number of genes are induced after L1 transfection into CRC cells by a mechanism involving the cytoskeletal protein ezrin and the NF‐ĸB pathway. When studying the changes in gene expression in CRC cells overexpressing L1 in which ezrin levels were suppressed by shRNA to ezrin, we discovered the collagen‐modifying enzyme lysyl hydroxylase 2 (PLOD2) among these genes. We found that increased PLOD2 expression was required for the cellular processes conferred by L1, including enhanced proliferation, motility, tumorigenesis and liver metastasis, since the suppression of endogenous PLOD2 expression, or its enzymatic activity, blocked the enhanced tumor-igenic properties conferred by L1. The mechanism involved in increased PLOD2 expression by L1 involves ezrin signaling and PLOD2 that affect the SMAD2/3 pathway. We found that PLOD2 is localized in the colonic crypts in the stem cell compartment of the normal mucosa and is found at increased levels in invasive areas of the tumor and, in some cases, throughout the tumor tissue. The therapeutic strategies to target PLOD2 expression might provide a useful approach for CRC treat-ment.
Authors with CRIS profile
Thomas Brabletz
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Involved external institutions
Israel (IL)How to cite
APA:
Cheriyamundath, S., Kumar, A., Gavert, N., Brabletz, T., & Ben‐ze’ev, A. (2021). The collagen‐modifying enzyme plod2 is induced and required during l1‐mediated colon cancer progression. International Journal of Molecular Sciences, 22(7). https://doi.org/10.3390/ijms22073552
MLA:
Cheriyamundath, Sanith, et al. "The collagen‐modifying enzyme plod2 is induced and required during l1‐mediated colon cancer progression." International Journal of Molecular Sciences 22.7 (2021).
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