Genomic amplification and functional dependency of the gamma actin gene actg1 in uterine cancer

Camden Richter, David Mayhew, Jonathan P. Rennhack, Jonathan So, Elizabeth H. Stover, Justin H. Hwang, Danuta Szczesna-Cordary

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we investigated dysregulation of nine sarcomeric and cytoskeletal genes across 20 cancer lineages. We found that uterine cancers harbored the highest frequencies of amplification and overexpression of the gamma actin gene, ACTG1. Each of the four subtypes of uterine cancers, mixed endometrial carcinomas, serous carcinomas, endometroid carcinomas, and carcinosarcomas harbored between 5~20% of ACTG1 gene amplification or overexpression. Clinically, patients with ACTG1 gains had a poor prognosis. ACTG1 gains showed transcriptional patterns that reflect activation of oncogenic signals, repressed response to innate immunity, or immunotherapy. Functionally, the CRISPR-CAS9 gene deletion of ACTG1 had the most robust and consistent effects in uterine cancer cells relative to 20 other lineages. Overall, we propose that ACTG1 regulates the fitness of uterine cancer cells by modulating cell-intrinsic properties and the tumor microenvironment. In summary, the ACTG1 functions relative to other actomyosin genes support the notion that it is a potential biomarker and a target gene in uterine cancer precision therapies.

Original languageEnglish (US)
Article number8690
Pages (from-to)1-15
Number of pages15
JournalInternational journal of molecular sciences
Volume21
Issue number22
DOIs
StatePublished - Nov 2 2020

Keywords

  • ACTG1
  • Cytoskeleton genes
  • Gene dysregulation in cancer
  • Uterine cancer

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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