Investigator

Adi Kimchi

Professor · Weizmann Institute of Science, Department of Molecular Genetics

AKAdi Kimchi
Papers(1)
Loss of EIF4G2 mediat…
Collaborators(1)
Ruth Scherz-Shouval
Institutions(1)
Weizmann Institute Of…

Papers

Loss of EIF4G2 mediates aggressiveness in distinct human endometrial cancer subpopulations with poor survival outcome in patients

Abstract The non-canonical translation initiation factor EIF4G2 plays essential roles in cellular stress responses via translation of selective mRNA cohorts. Currently there is limited and conflicting information regarding its involvement in cancer development and progression. Here we assessed its role in endometrial cancer (EC), in a cohort of 280 EC patients across different types, grades, and stages, and found that low EIF4G2 expression highly correlated with poor overall- and recurrence-free survival in Grade 2 EC patients, monitored over a period of up to 12 years. To establish a causative connection between low EIF4G2 expression and cancer progression, we stably knocked-down EIF4G2 in two human EC cell lines in parallel. EIF4G2 depletion resulted in increased resistance to conventional therapies and increased the prevalence of molecular markers for aggressive cell subsets, altering their transcriptional and proteomic landscapes. Prominent among the proteins with decreased abundance were Kinesin-1 motor proteins, KIF5B and KLC1, 2, 3. Multiplexed imaging of the EC patient tumor cohort showed a correlation between decreased expression of the kinesin proteins, and poor survival in patients with tumors of certain grades and stages. These findings reveal potential novel biomarkers for Grade 2 EC with ramifications for patient stratification and therapeutic interventions.

167Works
1Papers
1Collaborators

Positions

1997–

Professor

Weizmann Institute of Science · Department of Molecular Genetics

2011–

Chair, Council of Professors at Weizmann Institute of Science

Weizmann Institute of Science

2001–

Head

Weizmann Institute of Science · Department of Molecular Genetics

1988–

Associate Professor

Weizmann Institute of Science · Department of Molecular Genetics

1982–

Senior Scientist

Weizmann Institute of Science · Department of Molecular Genetics and Virology

1981–

Scientist

Weizmann Institute of Science · Department of Virology

Education

1981

Post-doctoral Fellow

Weizmann Institute of Science · Department of Virology

1977

PhD

Tel Aviv University · Department of Microbiology

1969

MSc

Tel Aviv University · Department of Microbiology

Keywords
programmed cell deathautophagycap-independent translationDAP5/EIF4G2DAPK/DAPK1