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PP4R1 accelerates the malignant progression of NSCLC via up-regulating HSPA6 expression and HSPA6-mediated ER stress

Xunxia Zhu1, Xiaoyu Chen1, Xiaoyong Shen1

  • 1Department of Thoracic Surgery, Affiliated Huadong Hospital, Fudan University, Shanghai, China.

Biochimica Et Biophysica Acta. Molecular Cell Research
|September 22, 2023
PubMed

Insights

Protein phosphatase 4 regulatory subunit 1 (PP4R1) promotes non-small cell lung cancer (NSCLC) progression by upregulating HSPA6 and activating endoplasmic reticulum stress. This finding offers new insights into NSCLC development and potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Protein phosphatase 4 (PP4) is crucial in tumor development.
  • The specific role of PP4's regulatory subunit 1 (PP4R1) in lung cancer is unclear.
  • Non-small cell lung cancer (NSCLC) is a major global health concern.

Purpose of the Study:

  • To investigate the function and mechanism of PP4R1 in non-small cell lung cancer (NSCLC) development.
  • To analyze the clinical significance of PP4R1 in NSCLC patients.
  • To elucidate the molecular pathways regulated by PP4R1 in NSCLC.

Main Methods:

  • TCGA database analysis using UALCAN for clinical correlation.
  • In vitro cellular experiments assessing proliferation, colony growth, migration, and invasion.
  • In vivo animal models to evaluate tumor growth and metastasis.
  • Bioinformatics analysis including RNA-sequencing and gene enrichment analysis.

Main Results:

  • PP4R1 mRNA overexpression correlates with poor prognosis in NSCLC.
  • PP4R1 overexpression enhances NSCLC cell proliferation, migration, invasion, and tumor growth in vivo.
  • PP4R1 upregulates heat shock protein 70 (HSP70) family genes, notably HSPA6.
  • HSPA6 overexpression mimics PP4R1's oncogenic effects and activates endoplasmic reticulum (ER) stress.

Conclusions:

  • PP4R1 drives NSCLC malignant progression.
  • PP4R1 exerts its effects by upregulating HSPA6 expression.
  • The PP4R1-HSPA6 axis activates endoplasmic reticulum stress, contributing to NSCLC pathogenesis.
Keywords:
ER stressHSPA6NSCLCPP4R1

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