TY - JOUR
T1 - Sox2 is an oncogenic driver of small-cell lung cancer and promotes the classic neuroendocrine subtype
AU - Voigt, Ellen
AU - Wallenburg, Madeline
AU - Wollenzien, Hannah
AU - Thompson, Ethan
AU - Kumar, Kirtana
AU - Feiner, Joshua
AU - McNally, Moira
AU - Friesen, Hunter
AU - Mukherjee, Malini
AU - Afeworki, Yohannes
AU - Kareta, Michael S.
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research
PY - 2021/12
Y1 - 2021/12
N2 - Although many cancer prognoses have improved in the past 50 years due to advancements in treatments, there has been little improvement in therapies for small-cell lung cancer (SCLC). One promising avenue to improve treatment for SCLC is to understand its underlying genetic alterations that drive its formation, growth, and cellular heterogeneity. RB1 loss is one key driver of SCLC, and RB1 loss has been associated with an increase in pluripotency factors such as SOX2. SOX2 is highly expressed and amplified in SCLC and has been associated with SCLC growth. Using a genetically engineered mouse model, we have shown that Sox2 is required for efficient SCLC formation. Furthermore, genome-scale binding assays have indicated that SOX2 can regulate key SCLC pathways such as NEUROD1 and MYC. These data suggest that SOX2 can be associated with the switch of SCLC from an ASCL1 subtype to a NEUROD1 subtype. Understanding this genetic switch is key to understanding such processes as SCLC progression, cellular heterogeneity, and treatment resistance.
AB - Although many cancer prognoses have improved in the past 50 years due to advancements in treatments, there has been little improvement in therapies for small-cell lung cancer (SCLC). One promising avenue to improve treatment for SCLC is to understand its underlying genetic alterations that drive its formation, growth, and cellular heterogeneity. RB1 loss is one key driver of SCLC, and RB1 loss has been associated with an increase in pluripotency factors such as SOX2. SOX2 is highly expressed and amplified in SCLC and has been associated with SCLC growth. Using a genetically engineered mouse model, we have shown that Sox2 is required for efficient SCLC formation. Furthermore, genome-scale binding assays have indicated that SOX2 can regulate key SCLC pathways such as NEUROD1 and MYC. These data suggest that SOX2 can be associated with the switch of SCLC from an ASCL1 subtype to a NEUROD1 subtype. Understanding this genetic switch is key to understanding such processes as SCLC progression, cellular heterogeneity, and treatment resistance.
UR - http://www.scopus.com/inward/record.url?scp=85120807380&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85120807380&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-20-1006
DO - 10.1158/1541-7786.MCR-20-1006
M3 - Article
C2 - 34593608
AN - SCOPUS:85120807380
SN - 1541-7786
VL - 19
SP - 2015
EP - 2025
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 12
ER -