<p>Figure S1. Sorting of CD24highCD44lowEPCAMhigh tumor propagating cells.</p>
Funding
Nebraska Department of Health and Human Services (Nebraska DHHS)
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...National Institute of General Medical Sciences (NIGMS)
United States Department of Health and Human Services
Find out more...U.S. Department of Defense (DOD)
ARTICLE ABSTRACT
Small cell lung carcinoma (SCLC) tumors are heterogeneous, with a subpopulation of cells primed for tumor initiation. In this study, we show that kinase suppressor of Ras 2 (KSR2) promotes the self-renewal and clonogenicity of SCLC cells. KSR2 is a molecular scaffold that promotes Raf/MEK/ERK signaling. KSR2 is preferentially expressed in the ASCL1 subtype of SCLC (SCLC-A) tumors and is expressed in pulmonary neuroendocrine cells, one of the identified cells of origin for SCLC-A tumors. The expression of KSR2 in SCLC and pulmonary neuroendocrine cells was previously unrecognized and serves as a novel model for understanding the role of KSR2-dependent signaling in normal and malignant tissues. Disruption of KSR2 in SCLC-A cell lines inhibits the colony-forming ability of tumor-propagating cells in vitro and their tumor-initiating capacity in vivo. The effect of KSR2 depletion on self-renewal and clonogenicity is dependent on the interaction of KSR2 with ERK. These data indicate that the expression of KSR2 is an essential driver of SCLC-A tumor–propagating cell function and therefore may play a role in SCLC tumor initiation. These findings shed light on a novel effector promoting initiation of SCLC-A tumors and a potential subtype-specific therapeutic target.
Manipulation of the molecular scaffold KSR2 in SCLC-A cells reveals its contribution to self-renewal, clonogenicity, and tumor initiation.
