LASP1 promotes proliferation, metastasis, invasion in head and neck squamous cell carcinoma and through direct interaction with HSPA1A

J Cell Mol Med. 2020 Jan;24(2):1626-1639. doi: 10.1111/jcmm.14854. Epub 2019 Dec 2.

Abstract

LIM and SH3 protein 1 (LASP1) is a specific focal adhesion protein that promotes metastasis in a variety of tumours. However, its role in head and neck squamous cell carcinoma (HNSCC) has not been fully validated. The purpose of this study was to analyse the interaction of LASP1 and its binding partner in HNSCC. The expression of LASP1 and HSPA1A in HNSCC was analysed by real-time PCR and Western blot. The effects of LASP1 on the biology behaviour of HNSCC cell lines were observed in vivo and in vitro. Co-immunoprecipitation analysis was performed to confirm the interaction between LASP1 and HSPA1A. LASP1 was highly expressed in HNSCC and associated with poor prognosis for patients. LASP1 also promoted cell proliferation, colony formation, invasion and cell cycle G2/M phase transition. Heat shock protein family A member 1A (HSPA1A) is identified as a chaperone protein of LASP1 and co-localized in the cytoplasm. HSPA1A positively regulates the interaction of LASP1 with P-AKT and enhances the malignant behaviour of HNSCC cells. LASP1 and HSPA1A are both up-regulated in HNSCC, and directly binds to each other. Double inhibition of LASP1 and HSPA1A expression may be an effective method for the treatment of HNSCC.

Keywords: HNSCC; HSPA1A; LASP1; metastasis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cohort Studies
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology*
  • Humans
  • LIM Domain Proteins / genetics
  • LIM Domain Proteins / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphorylation
  • Prognosis
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / pathology*
  • Up-Regulation / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA1A protein, human
  • LASP1 protein, human
  • LIM Domain Proteins
  • Proto-Oncogene Proteins c-akt

Associated data

  • GENBANK/NM 001271608.1