Therapeutic Targeting of Metadherin Suppresses Colorectal and Lung Cancer Progression and Metastasis
Abstract
Colorectal and lung cancers account for one-third of all cancer-related deaths worldwide. Previous studies suggested that metadherin (MTDH) is involved in the development of colorectal and lung cancers. However, how MTDH regulates the pathogenesis of these cancers remains largely unknown. Using genetically modified mouse models of spontaneous colorectal and lung cancers, we found that MTDH promotes cancer progression by facilitating Wnt activation and by inducing cytotoxic T-cell exhaustion, respectively. Moreover, we developed locked nucleic acid-modified (LNA) MTDH antisense oligonucleotides (ASO) that effectively and specifically suppress MTDH expression in vitro and in vivo. Treatments with MTDH ASOs in mouse models significantly attenuated progression and metastasis of colorectal, lung, and breast cancers. Our study opens a new avenue for developing therapies against colorectal and lung cancers by targeting MTDH using LNA-modified ASO.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 15, 2021
- Source ID
- 10.1158/0008-5472.can-20-1876
Entities
People
- Frank Jaschinski
- John F. Jin
- Liling Wan
- Michelle Rowicki
- Min Yuan
- Minhong Shen
- Richard Klar
- Shanshan Xie
- Sven Michel
- Tianhua Zhou
- Xiang Hang
- Xin Lu
- Yibin Kang
- Yong Wei
Organizations
- American Cancer Society
- Princeton University
- Rutgers University
- Susan G. Komen for the Cure
- United States Department of Defense
- University of Toronto
- Zhejiang University
- Zhejiang University School of Medicine