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Journal of Cancer Research and Clinical Oncology

Erschienen in:

17.11.2020 | Original Article – Cancer Research

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

verfasst von: Kelly L. Hamilton, Stephanie A. Sheehan, Edward P. Retzbach, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Premalatha Balachandran, Gary S. Goldberg

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 2/2021

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Abstract

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.

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Titel: Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways
verfasst von: Kelly L. Hamilton
Stephanie A. Sheehan
Edward P. Retzbach
Clinton A. Timmerman
Garret B. Gianneschi
Patrick J. Tempera
Premalatha Balachandran
Gary S. Goldberg
Publikationsdatum: 17.11.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 2/2021
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03456-8

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