Guan Chen
Medical College of Wisconsin, USA
Title: Targeting triple-negative breast cancer by inhibiting cancer stem-like cell (CSC) expansion
Biography
Biography: Guan Chen
Abstract
Triple negative breast cancer (TNBC) is highly progressive and lacks established targets for therapeutic intervention. p38g mitogen-activated protein kinase (MAPK) (gene name: MAPK12) is overexpressed in TNBC but how overexpressed p38g contributes to TNBC remains unknown. Here we show that p38g activation promotes TNBC development and progression by stimulating cancer stem-like cell (CSC) expansion and may serve as a novel therapeutic target for TNBC. p38g silencing in TNBC cells inhibits mammosphere formation and reduces levels of key CSC drivers’ expression including Nanog, Oct3/4, and Sox2. Moreover, p38g MAPK-forced expression alone is sufficient to stimulate CSC expansion and to induce malignant transformation with a phenotype resembling to TNBC in vitro and in vivo. Furthermore, p38g depends on its activity to stimulate CSC expansion and breast cancer progression, indicating a therapeutic opportunity by application of its pharmacological inhibitor. Indeed, the non-toxic p38g specific pharmacological inhibitor pirfenidone selectively inhibits TNBC growth in vitro and/or in vivo and significantly decreases CSC population. Mechanistically, p38g stimulates Nanog expression through AP-1 via interaction with c-Jun. These results together demonstrate that p38g drives TNBC development and progression and may be thus a novel therapeutic target by stimulating CSC expansion. Inhibiting p38g activity with pirfenidone may be a novel strategy for the treatment of TNBC