Xiujuan Li1, Jing Liu1, Hong Sun1, Yong Zou2, Juan Chen3, Yichun Chen4, Cheng Chen1, Xuan Wu1. 1. Departmen of Geriatrics, Wuhan NO. 1 Hospital, Wuhan, Hubei, China. 2. Department of Emergency, Wuhan Medical Emergency Center, Wuhan, Hubei-China. 3. Supervision of Department, Wuhan Hankou Hospital-Wuhan, Hubei, China. 4. Department of Digestive, Wuhan NO. 8 Hospital, Wuhan, Hubei, China.
Abstract
BACKGROUND: Recent studies showed that sushi repeat containing protein X linked 2 (SRPX2) could participate in the development of various malignant tumors. However, its role in non-small cell lung cancer (NSCLC) was unknown. The aim of the study was to prospectively investigate the role of SRPX2 in NSCLC cell proliferation, migration and invasion and reveal the underlying mechanism. MATERIAL AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry - IHC) were used to measure detect the mRNA and protein levels, respectively, in NSCLC tissues and cell lines. Cell Counting Kit-8 (CCK-8), colony formation, wound healing and transwell assays were utilized to assess cell proliferation, migration and invasion. In vivo subcutaneous xenograft tumor model was established to detect the tumorigenic function of SRPX2, and IHC assay was performed to measure protein expression. RESULTS: SRPX2 expression was upregulated in NSCLC tissues and cell lines, and positively correlated with tumor size, lymph node metastasis, distant metastasis and clinical stage. High SRPX2 expression also predicted poor prognosis. In vitro experiments indicated that overexpression of SRPX2 promoted the proliferation, migration, and invasion of SPC-A1 cells while knockdown of SRPX2 caused the opposite effects in A549 cells. Specifically, SRPX2 activated FAK/SRC/ERK pathway and its downstream effectors and promoted epithelial-mesenchymal transition (EMT). CONCLUSION: Taken together, our findings revealed a functional role of SRPX2 in NSCLC cell proliferation, migration and invasion. The underlying mechanism was, at least partially, the activation of FAK/SRC/ERK pathway. This study provides the molecular basis for targeting SRPX2 in potential clinical application for NSCLC.
BACKGROUND: Recent studies showed that sushi repeat containing protein X linked 2 (SRPX2) could participate in the development of various malignant tumors. However, its role in non-small cell lung cancer (NSCLC) was unknown. The aim of the study was to prospectively investigate the role of SRPX2 in NSCLC cell proliferation, migration and invasion and reveal the underlying mechanism. MATERIAL AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry - IHC) were used to measure detect the mRNA and protein levels, respectively, in NSCLC tissues and cell lines. Cell Counting Kit-8 (CCK-8), colony formation, wound healing and transwell assays were utilized to assess cell proliferation, migration and invasion. In vivo subcutaneous xenograft tumor model was established to detect the tumorigenic function of SRPX2, and IHC assay was performed to measure protein expression. RESULTS:SRPX2 expression was upregulated in NSCLC tissues and cell lines, and positively correlated with tumor size, lymph node metastasis, distant metastasis and clinical stage. High SRPX2 expression also predicted poor prognosis. In vitro experiments indicated that overexpression of SRPX2 promoted the proliferation, migration, and invasion of SPC-A1 cells while knockdown of SRPX2 caused the opposite effects in A549 cells. Specifically, SRPX2 activated FAK/SRC/ERK pathway and its downstream effectors and promoted epithelial-mesenchymal transition (EMT). CONCLUSION: Taken together, our findings revealed a functional role of SRPX2 in NSCLC cell proliferation, migration and invasion. The underlying mechanism was, at least partially, the activation of FAK/SRC/ERK pathway. This study provides the molecular basis for targeting SRPX2 in potential clinical application for NSCLC.
Authors: Tarana Arman; J Allen Baron; Katherine D Lynch; Laura A White; Johnny Aldan; John D Clarke Journal: Toxicology Date: 2021-11-02 Impact factor: 4.221