Oncogenic Ras/squamous cell carcinoma antigen signaling pathway activation promotes invasiveness and lymph node metastases in papillary thyroid carcinoma

Dingyuan Luo, Ying Liu, Shaojian Lin, Langping Tan, Zehu Du, Miaoyun Long, Yue Zhu, Xinzhi Peng, Weixing Zong, Gerardo Mackenzie, Honghao Li, Nengtai Ouyang

Research output: Contribution to journalArticle

Abstract

Papillary thyroid carcinoma (PTC) is a type of cancer with one of the fastest increasing incidences worldwide. However, the therapeutic choices for PTC patients are limited and it is critical to further understand the molecular pathology underlying this disease. Squamous cell carcinoma antigens (SCCAs) are overexpressed in many tumors and participate in tumorigenesis. However, their roles in PTC are incompletely understood. Therefore, this study investigated the role of SCCA in PTC, evaluating its expression, its clinical implications and prognostic significance in PTC patient samples, as well as its function in vitro and in vivo, using a thyroid cancer cell line in which SCCA levels have been knocked down or overexpressed. In this study, SCCA expression levels were measured by immunohistochemistry (IHC) in non-cancerous and tumor tissues. Kaplan-Meier analyses assessed the survival in PTC patients. MTT assay, western blot analysis, invasion assay and xenograft tumor assay were used to calculate cell proliferation, migration, invasion and tumor growth. Our results showed that SCCA was overexpressed in PTC tissues and was correlated with the clinical stage of PTC. Patients with high SCCA expression had lower overall survival (OS), disease-free survival (DFS), lymph node recurrence-free survival (LNRFS), and distant recurrence-free survival (DRFS), compared to patients expressing low level of the SCCA protein. SCCA knockdown suppressed thyroid cancer cell proliferation, invasion and reduced xenograft tumor growth, whereas SCCA overexpression increased cell proliferation, invasion and xenograft tumor growth. Mechanistically, the activation of Ras increased SCCA expression, and SCCA expression was positively correlated with Ras levels in the PTC tissues. In conclusion, SCCA protein is overexpressed in PTC and may represent a predictive prognostic factor for PTC patients. Furthermore, activation of the Ras/SCCA pathway plays an important role in promoting tumor growth, invasion and metastasis in PTC.

Original languageEnglish (US)
Pages (from-to)1253-1263
Number of pages11
JournalOncology Reports
Volume41
Issue number2
DOIs
StatePublished - Feb 1 2019

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Keywords

  • Invasion
  • Metastasis
  • Papillary thyroid carcinoma
  • Ras
  • SCCA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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