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
5939 - Matrix metalloproteinases and their tissue inhibitors genes abnormal DNA methylation in breast cancer
Presenter: Olga Simonova
Session: Poster Display session 1
Resources:
Abstract
2703 - Uveal melanoma cell lines depend on multiple signaling pathways for survival
Presenter: John Park
Session: Poster Display session 1
Resources:
Abstract
4849 - XAF1 and ZNF313 complex stimulates ER stress-induced apoptosis via direct GRP78 inhibition.
Presenter: Sungchan Jang
Session: Poster Display session 1
Resources:
Abstract
4801 - XAF1 assembles a destructive complex to induce BRCA1-mediated apoptosis via suppressing ERa and switching estrogen function
Presenter: Seung-hun Jang
Session: Poster Display session 1
Resources:
Abstract
3416 - Cancer associated fibroblasts promote cancer progression via Wnt2 secretion in colorectal cancer
Presenter: Hideaki Karasawa
Session: Poster Display session 1
Resources:
Abstract
4273 - Paired-related homeobox 1 overexpression promotes invasion and metastasis and is a prognostic factor for worse disease-free survival in patients with lung cancer
Presenter: Jung-jyh Hung
Session: Poster Display session 1
Resources:
Abstract
4241 - LncRNA-GC1 contributes to gastric cancer chemo-resistance through inhibition of miR-551b-3p and the overexpression of dysbindin
Presenter: Xin Guo
Session: Poster Display session 1
Resources:
Abstract
5388 - GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
Presenter: Pietro Paolo Vitiello
Session: Poster Display session 1
Resources:
Abstract
5208 - Characterisation of growth hormone signal transduction in primary melanoma cell lines
Presenter: Karla Sousa
Session: Poster Display session 1
Resources:
Abstract
3156 - LAPTM5 protein can regulate TGF-β mediated MAPK and Smad signaling pathways in ovarian cancer cell
Presenter: Yan Gao
Session: Poster Display session 1
Resources:
Abstract