TY - JOUR
T1 - Oncogenic Ras/squamous cell carcinoma antigen signaling pathway activation promotes invasiveness and lymph node metastases in papillary thyroid carcinoma
AU - Luo, Dingyuan
AU - Liu, Ying
AU - Lin, Shaojian
AU - Tan, Langping
AU - Du, Zehu
AU - Long, Miaoyun
AU - Zhu, Yue
AU - Peng, Xinzhi
AU - Zong, Weixing
AU - Mackenzie, Gerardo
AU - Li, Honghao
AU - Ouyang, Nengtai
PY - 2019/2/1
Y1 - 2019/2/1
N2 - 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.
AB - 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.
KW - Invasion
KW - Metastasis
KW - Papillary thyroid carcinoma
KW - Ras
KW - SCCA
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UR - http://www.scopus.com/inward/citedby.url?scp=85058898998&partnerID=8YFLogxK
U2 - 10.3892/or.2018.6895
DO - 10.3892/or.2018.6895
M3 - Article
C2 - 30535496
AN - SCOPUS:85058898998
VL - 41
SP - 1253
EP - 1263
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 2
ER -