Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells

Mara Artibani; Kenta Masuda; Zhiyuan Hu; Pascal C. Rauher; Garry Mallett; Nina Wietek; Matteo Morotti; Kay Chong; Mohammad KaramiNejadRanjbar; Christos E. Zois; Sunanda Dhar; Salma El-Sahhar; Leticia Campo; Sarah P. Blagden; Stephen Damato; Pubudu N. Pathiraja; Shibani Nicum; Fergus Gleeson; Alexandros Laios; Abdulkhaliq Alsaadi; Laura Santana Gonzalez; Takeshi Motohara; Ashwag Albukhari; Zhen Lu; Robert C. Bast; Adrian L. Harris; Christer S. Ejsing; Robin W. Klemm; Christopher Yau; Tatjana Sauka-Spengler; Ahmed Ashour Ahmed

doi:10.1172/jci.insight.147929

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Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells

Journal article

Open access

Peer reviewed

Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells

Mara Artibani, Kenta Masuda, Zhiyuan Hu, Pascal C. Rauher, Garry Mallett, Nina Wietek, Matteo Morotti, Kay Chong, Mohammad KaramiNejadRanjbar, Christos E. Zois, …

JCI insight, Vol.6(11)

08/06/2021

DOI: https://doi.org/10.1172/jci.insight.147929

PMID: 33945502

Abstract

Fatty acid oxidation

gynecology

Obstetrics

Oncology

Similar to tumor-initiating cells (TICs), minimal residual disease (MRD) is capable of reinitiating tumors and causing recurrence. However, the molecular characteristics of solid tumor MRD cells and drivers of their survival have remained elusive. Here we performed dense multiregion transcriptomics analysis of paired biopsies from 17 ovarian cancer patients before and after chemotherapy. We reveal that while MRD cells share important molecular signatures with TICs, they are also characterized by an adipocyte-like gene expression signature and a portion of them had undergone epithelial-mesenchymal transition (EMT). In a cell culture MRD model, MRD-mimic cells showed the same phenotype and were dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings identify EMT and FAO as attractive targets to eradicate MRD in ovarian cancer and make a compelling case for the further testing of FAO inhibitors in treating MRD.

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Title: Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells
Creators - without role: Mara Artibani - The University of Texas MD Anderson Cancer Center
Kenta Masuda - The University of Texas MD Anderson Cancer Center
Zhiyuan Hu - The University of Texas MD Anderson Cancer Center
Pascal C. Rauher - The University of Texas MD Anderson Cancer Center
Garry Mallett - The University of Texas MD Anderson Cancer Center
Nina Wietek - The University of Texas MD Anderson Cancer Center
Matteo Morotti - The University of Texas MD Anderson Cancer Center
Kay Chong - The University of Texas MD Anderson Cancer Center
Mohammad KaramiNejadRanjbar - The University of Texas MD Anderson Cancer Center
Christos E. Zois - The University of Texas MD Anderson Cancer Center
Sunanda Dhar - The University of Texas MD Anderson Cancer Center
Salma El-Sahhar - The University of Texas MD Anderson Cancer Center
Leticia Campo - The University of Texas MD Anderson Cancer Center
Sarah P. Blagden - The University of Texas MD Anderson Cancer Center
Stephen Damato - The University of Texas MD Anderson Cancer Center
Pubudu N. Pathiraja - The University of Texas MD Anderson Cancer Center
Shibani Nicum - The University of Texas MD Anderson Cancer Center
Fergus Gleeson - The University of Texas MD Anderson Cancer Center
Alexandros Laios - The University of Texas MD Anderson Cancer Center
Abdulkhaliq Alsaadi - The University of Texas MD Anderson Cancer Center
Laura Santana Gonzalez - The University of Texas MD Anderson Cancer Center
Takeshi Motohara - The University of Texas MD Anderson Cancer Center
Ashwag Albukhari - The University of Texas MD Anderson Cancer Center
Zhen Lu - The University of Texas MD Anderson Cancer Center
Robert C. Bast - The University of Texas MD Anderson Cancer Center
Adrian L. Harris - The University of Texas MD Anderson Cancer Center
Christer S. Ejsing - The University of Texas MD Anderson Cancer Center
Robin W. Klemm - The University of Texas MD Anderson Cancer Center
Christopher Yau - The University of Texas MD Anderson Cancer Center
Tatjana Sauka-Spengler - The University of Texas MD Anderson Cancer Center
Ahmed Ashour Ahmed - The University of Texas MD Anderson Cancer Center
Publication Details: JCI insight, Vol.6(11)
Publisher: American Society for Clinical Investigation
Grant note: HMR01843 / ; VKR023439 / ; R54-A5858 / ; VKR023179 / VILLUM Center for Bioanalytical Sciences P50CA217685 / MD Anderson Specialized Program of Research Excellence in Ovarian Cancer HER00070 / ;
Identifiers: 9935622808331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article