2. Academic Validation
  3. SURF4 inhibits autophagy to enhance lung adenocarcinoma progression and stemness through Hedgehog pathway regulation

SURF4 inhibits autophagy to enhance lung adenocarcinoma progression and stemness through Hedgehog pathway regulation

  • Tissue Cell. 2026 Jan 26:100:103351. doi: 10.1016/j.tice.2026.103351.
Junzheng Zhou 1,  Shiwei Nie 1,  Xiaodong Zheng 1,  Xudong Wei 1,  Jinrui Zhang 2,  Xiaojuan Shen 1,  Weimin Zhang 3
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, China.
  • 2 Supply House, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, China.
  • 3 Department of Thoracic Surgery, Anyang Tumor Hospital, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, China. Electronic address: [email protected].
PMID: 41637921 DOI: 10.1016/j.tice.2026.103351
Abstract

Background: Drug resistance, metastasis, and recurrence are major contributors to the poor survival rates of lung adenocarcinoma (LUAD) patients. Studies suggest that tumor stemness is a key driver of drug resistance, recurrence, and metastasis. Although Surfeit locus protein 4 (SURF4) has been shown to promote tumor cell stemness, the molecular mechanisms by which SURF4 regulates LUAD growth and stemness remain elusive.

Methods: Differentially expressed genes were identified using the TCGA-LUAD database to compare LUAD tissues with adjacent normal tissues, followed by experimental validation. qRT-PCR, CCK-8, and flow cytometry assays were used to assess the functional impact of SURF4. Tumor stemness was evaluated by sphere formation assays and Western blotting. In addition, GSEA combined with cellular experiments was employed to validate the mechanism underlying SURF4-mediated regulation of LUAD growth and stemness.

Results: There was abnormal upregulation of SURF4 in LUAD tissues and cells. Knockdown of SURF4 enhanced Autophagy and suppressed LUAD cell proliferation and stemness. Mechanistically, SURF4 was found to activate the Hedgehog pathway by facilitating Sonic Hedgehog (Shh) transport, thereby inhibiting Autophagy. Rescue experiments confirmed that SURF4's effects on LUAD growth and stemness were primarily mediated through this mechanism.

Conclusion: SURF4 promotes LUAD proliferation and maintains tumor stemness by suppressing Autophagy through Hedgehog pathway activation.

Keywords

Autophagy; Hedgehog pathway; Lung Adenocarcinoma; SURF4; Stemness.

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