American Association for Cancer Research
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Supplementary Table S1 from JARID1B Enables Transit between Distinct States of the Stem-like Cell Population in Oral Cancers

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posted on 2023-03-31, 00:31 authored by Nicole D. Facompre, Kayla M. Harmeyer, Xavier Sole, Sheheryar Kabraji, Zachary Belden, Varun Sahu, Kelly Whelan, Koji Tanaka, Gregory S. Weinstein, Kathleen T. Montone, Alexander Roesch, Phyllis A. Gimotty, Meenhard Herlyn, Anil K. Rustgi, Hiroshi Nakagawa, Sridhar Ramaswamy, Devraj Basu

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NIH

Instituto de Salud Carlos III

ACS

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ARTICLE ABSTRACT

The degree of heterogeneity among cancer stem cells (CSC) remains ill-defined and may hinder effective anti-CSC therapy. Evaluation of oral cancers for such heterogeneity identified two compartments within the CSC pool. One compartment was detected using a reporter for expression of the H3K4me3 demethylase JARID1B to isolate a JARID1Bhigh fraction of cells with stem cell–like function. JARID1Bhigh cells expressed oral CSC markers including CD44 and ALDH1 and showed increased PI3K pathway activation. They were distinguished from a fraction in a G0-like cell-cycle state characterized by low reactive oxygen species and suppressed PI3K/AKT signaling. G0-like cells lacked conventional CSC markers but were primed to acquire stem cell–like function by upregulating JARID1B, which directly mediated transition to a state expressing known oral CSC markers. The transition was regulated by PI3K signals acting upstream of JARID1B expression, resulting in PI3K inhibition depleting JARID1Bhigh cells but expanding the G0-like subset. These findings define a novel developmental relationship between two cell phenotypes that may jointly contribute to CSC maintenance. Expansion of the G0-like subset during targeted depletion of JARID1Bhigh cells implicates it as a candidate therapeutic target within the oral CSC pool. Cancer Res; 76(18); 5538–49. ©2016 AACR.