TY - JOUR
T1 - P21CIP1 promotes mammary cancer-initiating cells via activation of Wnt/TCF1/CyclinD1 signaling
AU - Benard, Outhiriaradjou
AU - Qian, Xia
AU - Liang, Huizhi
AU - Ren, Zuen
AU - Suyama, Kimita
AU - Norton, Larry
AU - Hazan, Rachel B.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Cancer stem cells (CSC) generate and sustain tumors due to tumor-initiating potential, resulting in recurrence or metastasis. We showed that knockout of the cell-cycle inhibitor, p21CIP1, in the PyMT mammary tumor model inhibits metastasis; however the mechanism remained unknown. Here, we show a pivotal role for p21 in potentiating a cancer stem-like phenotype. p21 knockout in PyMT mammary tumor cells caused dramatic suppression of CSC properties involving tumorsphere formation, ALDH1 activity, and tumor-initiating potential, which were in turn rescued by p21 overexpression into PyMT/p21 knockout cells. Interestingly, p21 knockout dramatically suppresses Wnt/b-catenin signaling activity, leading to striking inhibition of LEF1 and TCF1 expression. TCF1 knockdown in PyMT cells suppressed tumorsphere formation due to Cyclin D1 attenuation. These data demonstrate that p21 promotes a CSC-like phenotype via activation of Wnt/TCF1/Cyclin D1 signaling.
AB - Cancer stem cells (CSC) generate and sustain tumors due to tumor-initiating potential, resulting in recurrence or metastasis. We showed that knockout of the cell-cycle inhibitor, p21CIP1, in the PyMT mammary tumor model inhibits metastasis; however the mechanism remained unknown. Here, we show a pivotal role for p21 in potentiating a cancer stem-like phenotype. p21 knockout in PyMT mammary tumor cells caused dramatic suppression of CSC properties involving tumorsphere formation, ALDH1 activity, and tumor-initiating potential, which were in turn rescued by p21 overexpression into PyMT/p21 knockout cells. Interestingly, p21 knockout dramatically suppresses Wnt/b-catenin signaling activity, leading to striking inhibition of LEF1 and TCF1 expression. TCF1 knockdown in PyMT cells suppressed tumorsphere formation due to Cyclin D1 attenuation. These data demonstrate that p21 promotes a CSC-like phenotype via activation of Wnt/TCF1/Cyclin D1 signaling.
UR - http://www.scopus.com/inward/record.url?scp=85069264344&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069264344&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-18-1044
DO - 10.1158/1541-7786.MCR-18-1044
M3 - Article
C2 - 30967481
AN - SCOPUS:85069264344
SN - 1541-7786
VL - 17
SP - 1571
EP - 1581
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 7
ER -
