Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways
| Autor: | Gary S. Goldberg, Clinton A. Timmerman, Kelly L. Hamilton, Patrick J. Tempera, Edward P. Retzbach, Premalatha Balachandran, Garret B. Gianneschi, Stephanie A. Sheehan |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Transcription Genetic Smad Proteins Biology Article Transcriptome 03 medical and health sciences 0302 clinical medicine SOX2 Cell Movement Gene expression medicine Humans Maackia PDPN Transcription factor Wnt Signaling Pathway Squamous Cell Carcinoma of Head and Neck SOXB1 Transcription Factors JAK-STAT signaling pathway Cancer General Medicine medicine.disease Gene Expression Regulation Neoplastic stomatognathic diseases 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Mouth Neoplasms Signal transduction Plant Lectins Signal Transduction |
| Zdroj: | J Cancer Res Clin Oncol |
| ISSN: | 1432-1335 |
| Popis: | 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 thousand 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. |
| Databáze: | OpenAIRE |
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