Related Experiment Video

Updated: Oct 14, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
12:13

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

Published on: November 19, 2019

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SPP1 Promotes Enzalutamide Resistance and Epithelial-Mesenchymal-Transition Activation in Castration-Resistant

Xiaocong Pang1, Junling Zhang2, Xu He1

  • 1Department of Pharmacy, Peking University First Hospital, Beijing 100034, China.

Oxidative Medicine and Cellular Longevity
|November 1, 2021
PubMed

Insights

Secreted phosphoprotein 1 (SPP1) drives castration-resistant prostate cancer (CRPC) progression and drug resistance. Reducing SPP1 can improve treatment outcomes by enhancing drug sensitivity and inhibiting metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) presents significant treatment challenges due to metastasis and drug resistance.
  • Secreted phosphoprotein 1 (SPP1) is implicated in tumor inflammation and metastasis, and previously identified as a potential biomarker for metastatic CRPC (mCRPC).

Purpose of the Study:

  • To investigate the association of SPP1 expression with prognosis, survival, and metastatic potential in CRPC.
  • To explore the role of SPP1 in enzalutamide resistance and prostate cancer cell behavior (adhesion, migration, epithelial-mesenchymal-transition).
  • To elucidate the underlying molecular mechanisms regulated by SPP1 in CRPC progression.

Main Methods:

  • Bioinformatics analysis of multiple databases.
  • In vitro studies using prostate cancer cell lines with SPP1 overexpression or depletion.
  • Polymerase chain reaction (PCR), immunohistochemical staining, and western blot analysis.
  • Investigation of PI3K/AKT and ERK1/2 signaling pathways.

Main Results:

  • SPP1 upregulation correlates with advanced CRPC, poor prognosis, and enzalutamide resistance.
  • SPP1 knockdown enhances enzalutamide sensitivity and reduces prostate cancer cell invasion and migration.
  • SPP1 influences epithelial-mesenchymal-transition (EMT) and activates PI3K/AKT and ERK1/2 signaling pathways.

Conclusions:

  • SPP1 plays a critical role in CRPC progression, metastasis, and resistance to antiandrogen therapy.
  • Targeting SPP1 may offer a novel therapeutic strategy to overcome enzalutamide resistance and combat mCRPC.
  • SPP1's regulation of EMT and key signaling pathways highlights its significance in CRPC pathogenesis.

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