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 (ASOs) 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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Shen M,Xie S,Rowicki M,Michel S,Wei Y,Hang X,Wan L,Lu X,Yuan M,Jin JF,Jaschinski F,Zhou T,Klar R,Kang Ydoi
10.1158/0008-5472.CAN-20-1876subject
Has Abstractpub_date
2020-11-25 00:00:00eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-20-1876pub_type
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