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SIPA1L3 via its PDZ domain inhibits the tight junction-associated AMOT-Patj to promote a malignant phenotype in NSCLC

Lin Wang1, Bin-Xue Wang2, Rui Zhang2

  • 1Blood Transfusion Department, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong Province, PR China.

Medicine
|October 15, 2025
PubMed
Abstract

Insights

Signal-induced proliferation-associated 1 like 3 (SIPA1L3) promotes lung cancer growth and spread. This protein interacts with AMOT, suggesting SIPA1L3 as a potential therapeutic target for non-small cell lung cancer (NSCLC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Signal-induced proliferation-associated 1 like 3 (SIPA1L3) function in human carcinoma is largely unknown.
  • Limited data exists on SIPA1L3's role in non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • Investigate SIPA1L3 expression patterns in NSCLC.
  • Elucidate the functional role of SIPA1L3 in NSCLC progression.
  • Determine SIPA1L3's molecular interactions within lung cancer cells.

Main Methods:

  • Immunohistochemistry used to analyze SIPA1L3 distribution in NSCLC tissues.
  • Small interfering RNA (siRNA) employed to assess SIPA1L3's impact on cell proliferation and invasion in vitro and in vivo.
  • Western blotting and immunoprecipitation utilized to identify interactions between SIPA1L3, angiomotin (AMOT), and Pals1-associated tight junction protein.

Main Results:

  • SIPA1L3 is overexpressed in NSCLC tissues and correlates with clinicopathological features.
  • SIPA1L3 significantly affects cancer cell proliferation and invasion both in vitro and in vivo.
  • SIPA1L3 interacts with AMOT via its PDZ domain, disrupting AMOT's association with Pals1-associated tight junction protein and tight junctions.

Conclusions:

  • SIPA1L3 promotes lung cancer tumorigenesis through its interaction with AMOT.
  • The PDZ domain of SIPA1L3 is crucial for its oncogenic activity.
  • SIPA1L3 represents a novel therapeutic target for lung cancer due to its contribution to the malignant phenotype.
Keywords:
AMOTHippo pathwayNSCLCPatjSIPA1L3

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