Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways

J Cancer Res Clin Oncol. 2021 Feb;147(2):445-457. doi: 10.1007/s00432-020-03456-8. Epub 2020 Nov 17.


Purpose: Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined.

Methods: Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level.

Results: MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ-SMAD, JAK-STAT, and Wnt-βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil.

Conclusions: Taken together, results from this study indicate that MASL decreases activity of JAK-STAT, TGFβ-SMAD, and Wnt-βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.

Keywords: Chemotherapy; JAK–STAT; Lectin; Maackia amurensis; Oral cancer; Oral squamous cell carcinoma; Podoplanin; SMAD; Tgfβ.

MeSH terms

  • Cell Movement / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Maackia / chemistry*
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • Plant Lectins / pharmacology*
  • Plant Lectins / therapeutic use
  • SOXB1 Transcription Factors / genetics
  • Signal Transduction / drug effects
  • Smad Proteins / genetics
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Transcription, Genetic / drug effects
  • Wnt Signaling Pathway / drug effects


  • Plant Lectins
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Smad Proteins