Abstract 5132
Background
Hepatocyte growth factor (HGF) regulates cell motility, proliferation and morphology and has a crucial impact on the ability of tumors to metastasize. Tight Junctions (TJs) are the first barrier that cancer cells must overcome to metastasize. In previous studies, signal induced proliferation associated protein 1 (SIPA1) has been shown to be involved in the metastasis of tumors. Breast and prostate cancer cells exhibit reduced response to HGF after SIPA1 knock down which was concurrent with changes in the regulation of TJs. It appears that SIPA1 influence HGF mediated control of TJs in cancer cells. We aimed to discover the role of SIPA1 in the HGF-mediated regulation of TJs and metastatic spread in lung adenocarcinoma.
Methods
Expression of SIPA1 was measured in human lung tumor tissues (n = 148) together with adjacent background tissue (n = 148). IHC was performed to examine SIPA1 expression within a lung tissue microarray. In vitro cell function assays were carried out after knock down of SIPA1 in the A549 cell line with/without HGF. Related TJs protein expression was analyzed using qPCR and western blotting.
Results
Patients with lung cancer exhibited a higher expression level of SIPA1 in tumor compared with background tissues (n = 148, p = 0.0141). High expression of SIPA1 was associated with advanced T stage of lung cancer (T3 vs T1, p = 0.014) and poor prognosis (p = 0.0021). Moreover, knockdown of SIPA1 reduced the aggressive behavior and enhanced the barrier function of the A549 cells. The SIPA1 knockdown cells showed a decreased response after treatment with HGF in invasion, proliferation and barrier function assays. In addition, receptor of HGF (Met) and several TJ components such as JAM1, Claudin5, Claudin10, Claudin11 and Claudin20 had reduced expression, whilst others such as Claudin1, Claudin19 had increased expression after knockdown of SIPA1.
Conclusions
SIPA1 may act as a targeting molecule and a marker for prognosis in lung adenocarcinoma. It has an effect on pathways associated with aggressive behavior and barrier function in lung cancer cells. HGF induced malignant behavior of cancer cells requires the presence and influence of SIPA1, which can effect changes in cancer cell behavior by interacting with the TJ complex.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Tracey A. Martin - Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5255 - [18F]-FDG PET/CT in predicting PD-L1 status in nasopharyngeal carcinoma
Presenter: Liang Zhao
Session: Poster Display session 1
Resources:
Abstract
4910 - Expression of PD-L1 in Chinese Patients with Common Cancers
Presenter: Min Zheng
Session: Poster Display session 1
Resources:
Abstract
4227 - The clearance of EGF by tumor-associated macrophages is suppressed by chemotherapeutic agent cisplatin
Presenter: Irina Larionova
Session: Poster Display session 1
Resources:
Abstract
5222 - VHIO-300 and a thousand one nights, a tale of Precision Medicine
Presenter: Ginevra Caratù
Session: Poster Display session 1
Resources:
Abstract
5668 - Matched Whole-Genome Sequencing and Whole-Exome Sequencing with Circulating Tumor DNA (ctDNA) Analysis are complementary modalities in clinical practice
Presenter: Robin Imperial
Session: Poster Display session 1
Resources:
Abstract
5772 - Exploring the role of genes associated with familial cancer syndromes on the development of multiple primary tumors
Presenter: Atanaska Mitkova
Session: Poster Display session 1
Resources:
Abstract
4784 - Doxorubicin resistance: early and advanced tumors can use two different strategies based on initial and profound abnormalities in microRNA expression signature
Presenter: Volodymyr Halytskiy
Session: Poster Display session 1
Resources:
Abstract
3456 - From tumor transcriptomes to underlying cell type proportions to better predict prognosis and response to treatments
Presenter: Yuna Blum
Session: Poster Display session 1
Resources:
Abstract
4976 - Optimization of automated germline DNA extraction from non-tumoral formalin-fixed paraffin embedded (FFPE) tissues
Presenter: Omar Youssef
Session: Poster Display session 1
Resources:
Abstract
4242 - HIV, HBV and HCV screening practices in oncology: a cross-sectional interregional survey
Presenter: Isabelle Poizot-Martin
Session: Poster Display session 1
Resources:
Abstract