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Related Experiment Video

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CALR/HIF-1α Positive Feedback Loop Drives CALR Upregulation to Promote EMT-Mediated Bladder Cancer Progression via

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|March 5, 2026
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Summary

Calreticulin (CALR) drives bladder cancer progression via a novel feedback loop with HIF-1α, promoting tumor growth and metastasis. Sinapine, a natural compound, inhibits CALR, offering a potential new therapy for bladder cancer.

Keywords:
CALREMTHIF‐1αROSbladder cancertumor progression

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Calreticulin (CALR) is a key driver in myeloproliferative neoplasms (MPN) and a diagnostic biomarker.
  • The role and mechanisms of CALR in solid tumors, specifically bladder cancer (BLCA), are not well understood.

Purpose of the Study:

  • To investigate the role of CALR in bladder cancer (BLCA) progression.
  • To elucidate the molecular mechanisms by which CALR promotes BLCA.
  • To identify potential therapeutic strategies targeting CALR in BLCA.

Main Methods:

  • Analysis of CALR expression in BLCA tissues and correlation with patient prognosis.
  • Investigation of the CALR/HIF-1α feedback loop involving von Hippel-Lindau (VHL) protein.
  • Assessment of CALR's role in epithelial-mesenchymal transition (EMT) via reactive oxygen species (ROS) and AKT signaling.
  • In vitro and in vivo evaluation of Sinapine as a CALR inhibitor.

Main Results:

  • CALR expression is significantly elevated in BLCA and associated with poor prognosis.
  • A novel positive feedback loop between CALR and HIF-1α (stabilized by VHL) sustains high CALR levels in BLCA.
  • CALR promotes BLCA progression by inducing EMT through ROS accumulation and AKT pathway activation.
  • Sinapine effectively inhibits CALR and suppresses BLCA growth in vitro and in vivo.

Conclusions:

  • CALR plays a critical role in promoting bladder cancer progression through the CALR/HIF-1α feedback loop and EMT.
  • CALR is a potential prognostic biomarker for BLCA.
  • Targeted inhibition of CALR, for example with Sinapine, represents a promising therapeutic strategy for bladder cancer.