2026-01-16 北海道大学医学研究院
L1CAM-NF-κB経路の模式図
<関連情報>
- https://www.hokudai.ac.jp/news/2026/01/l1cam-nf-b.html
- https://www.hokudai.ac.jp/news/pdf/260116_pr2.pdf
- https://www.mdpi.com/2072-6694/18/2/198
L1CAMはNF-κBの活性化を通してヒト子宮体がんを促進する L1CAM Promotes Human Endometrial Cancer Via NF-κB Activation
Hiroyuki Kurosu,,Hiroshi Asano,Alaa-eldin Salah-eldin,Kazuya Hamada,Shugo Tanaka,Asuka Ishii,Issei Kawakita,Kentaro Kumagai,Kensuke Nakazono,Yuko Katayama,Rino Saito,Chihiro Terasaka,Sari Iwasaki,Satoshi Tanaka,Atsushi Niida,Hidemichi Watari and Koji Taniguchi
Cancers Published: 8 January 2026
DOI:https://doi.org/10.3390/cancers18020198
Simple Summary
The incidence and mortality rates of endometrial cancer are increasing, particularly in developed countries, and the prognosis for advanced cases has not improved. The L1 cell adhesion molecule (L1CAM) has been identified as a poor prognostic factor in human endometrial cancer, but the molecular mechanisms underlying its role in tumor progression remain unclear. We demonstrated that L1CAM knockdown and overexpression in human endometrial cancer cell lines promote progression from the G0/G1 phase and enhance cell proliferation. Furthermore, we showed that the L1CAM-NF-κB pathway is involved in these effects. Immunohistochemical staining confirmed a significant correlation between L1CAM expression and nuclear NF-κB positivity in human patient specimens. Additionally, combination therapy with cisplatin and an IKK inhibitor enhanced the antiproliferative effect, suggesting the involvement of this pathway in chemotherapy resistance. Our findings suggest that therapeutic strategies targeting the L1CAM-NF-κB pathway represent a promising treatment option for improving prognosis in L1CAM-positive human endometrial cancer.
Abstract
Background/Objectives: Endometrial cancer is one of the most common gynecological malignancies, with increasing incidence and mortality rates, particularly in developed countries. L1 cell adhesion molecule (L1CAM) has been identified as a poor prognostic factor for human endometrial cancer; however, the molecular mechanisms underlying its role in tumor progression remain unclear. Methods: We investigated the biological significance of L1CAM in human endometrial cancer using multiple cell lines. Functional analyses, including cell proliferation, cell cycle, and apoptosis assays, were performed after L1CAM knockdown or overexpression. Results: L1CAM promoted the transition of endometrial cancer cells from the G0/G1 phase and enhanced cell proliferation. L1CAM knockdown inhibited NF-κB signaling by reducing NF-κB (p65) phosphorylation and downregulating the expression of downstream targets such as TNF. Overexpression of constitutively active IKKβ restored the proliferation defect caused by L1CAM knockdown, supporting the role of NF-κB as a key downstream effector of L1CAM. Immunohistochemical analysis revealed a significant correlation between L1CAM expression and nuclear NF-κB (p65) positivity rates in human patient samples. Furthermore, combination therapy with cisplatin and an IKK inhibitor enhanced the anti-proliferative effect. Conclusions: Our study demonstrated that L1CAM promotes proliferation and chemotherapy resistance in human endometrial cancer through activation of the NF-κB signaling pathway. Therapeutic strategies targeting the L1CAM-NF-κB pathway may represent a promising treatment option for improving prognosis in L1CAM-positive human endometrial cancer.
