Molecular and cellular endocrinology · 2026
Hsp90α as a promising therapeutic target for suppressing tumor progression in Lactotroph PitNETs.
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Wu Jie, Zhou Zhengan, Ding Chongxue, Sun Hongjie, Xia Ming, Zhou Kai, Zhang Tingrong, Li Shaoshan
Аннотация
BACKGROUND: Aggressive Lactotroph Pituitary Neuroendocrine Tumors (Lactotroph PitNETs) usually exhibit invasive growth behavior and resistance to dopamine agonists, showing difficulty in radical treatment and a high recurrence rate. Heat shock protein 90α(Hsp90α),a pivotal isoform of the heat shock protein 90(Hsp90) family, acts as a central chaperone that stabilizes numerous oncoproteins driving tumor progression, but its role in Lactotroph PitNETs remains unclear.
OBJECTIVE: To study the effect of Hsp90α knockdown on the proliferation and invasiveness of Lactotroph PitNETs cells (MMQ).
METHODS: Hsp90α and EGFR expression was compared between 18 aggressive and 22 Non-Aggressive human Lactotroph PitNETs by IHC and immunofluorescence. MMQ rat lactosomatotroph cells were transduced with lentiviral shRNA targeting Hsp90α(shHsp90α). Cell proliferation (CCK8),apoptosis (Annexin-V/7-AAD flow cytometry), Prolactin (PRL) secretion (ELISA), migration and invasion (Transwell) were assessed. Western blotting evaluated EGFR,PRL,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR.
RESULTS: Aggressive Lactotroph PitNETs displayed higher Hsp90α and EGFR expression and showed a notable degree of spatial overlap. Hsp90α knockdown reduced EGFR,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR levels, decreased proliferation, increased apoptosis, lowered PRL secretion, and impaired migration and invasion.
CONCLUSIONS: Hsp90α knockdown simultaneously destabilizes EGFR and its downstream AKT/mTOR and ERK axes, resulting in multi-modal suppression of Lactotroph PitNETs invasion. Targeting Hsp90α may offer a novel therapeutic strategy for Aggressive Lactotroph PitNETs refractory to standard medical therapy.
OBJECTIVE: To study the effect of Hsp90α knockdown on the proliferation and invasiveness of Lactotroph PitNETs cells (MMQ).
METHODS: Hsp90α and EGFR expression was compared between 18 aggressive and 22 Non-Aggressive human Lactotroph PitNETs by IHC and immunofluorescence. MMQ rat lactosomatotroph cells were transduced with lentiviral shRNA targeting Hsp90α(shHsp90α). Cell proliferation (CCK8),apoptosis (Annexin-V/7-AAD flow cytometry), Prolactin (PRL) secretion (ELISA), migration and invasion (Transwell) were assessed. Western blotting evaluated EGFR,PRL,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR.
RESULTS: Aggressive Lactotroph PitNETs displayed higher Hsp90α and EGFR expression and showed a notable degree of spatial overlap. Hsp90α knockdown reduced EGFR,AKT,ERK1/2,mTOR,p-AKT,p-ERK1/2 and p-mTOR levels, decreased proliferation, increased apoptosis, lowered PRL secretion, and impaired migration and invasion.
CONCLUSIONS: Hsp90α knockdown simultaneously destabilizes EGFR and its downstream AKT/mTOR and ERK axes, resulting in multi-modal suppression of Lactotroph PitNETs invasion. Targeting Hsp90α may offer a novel therapeutic strategy for Aggressive Lactotroph PitNETs refractory to standard medical therapy.