Therapeutic targeting of metadherin suppresses colorectal and lung cancer progression and metastasis

Minhong Shen, Shanshan Xie, Michelle Rowicki, Sven Michel, Yong Wei, Xiang Hang, Liling Wan, Xin Lu, Min Yuan, John F. Jin, Frank Jaschinski, Tianhua Zhou, Richard Klar, Yibin Kang

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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. Significance: This study provides new insights into the mechanism of MTDH in promoting colorectal and lung cancers, as well as genetic and pharmacologic evidence supporting the development of MTDH-targeting therapeutics.

Original languageEnglish (US)
Pages (from-to)1014-1025
Number of pages12
JournalCancer Research
Volume81
Issue number4
DOIs
StatePublished - Feb 15 2021

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Therapeutic targeting of metadherin suppresses colorectal and lung cancer progression and metastasis'. Together they form a unique fingerprint.

Cite this