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
5729 - Expression of mutant p53 affects cancer cell sensitivity to topotecan
Presenter: Rimma Mingaleeva
Session: Poster Display session 1
Resources:
Abstract
5725 - Breast cancer organoids a new tool for the prediction of drugs penetration and patient’outcome
Presenter: Giuseppina Roscigno
Session: Poster Display session 1
Resources:
Abstract
5680 - Aptamer-mediated exosomes detection for early breast cancer identification.
Presenter: Cristina Quintavalle
Session: Poster Display session 1
Resources:
Abstract
2460 - MicroRNA-181c promotes tamoxifen resistance in breast cancer cells via upregulation Akt/mTOR axis
Presenter: Alexander Scherbakov
Session: Poster Display session 1
Resources:
Abstract
3751 - Spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in tumor-immune milieu of infiltrating ductal carcinoma of the breast
Presenter: Sandhya Sreedharan
Session: Poster Display session 1
Resources:
Abstract
4664 - Large genomic rearrangements in BRCA1 and BRCA2 genes in the Portuguese population.
Presenter: Joao Pinto
Session: Poster Display session 1
Resources:
Abstract
4611 - Non-BRCA1/2 hereditary breast and ovarian cancer: findings from a multidisciplinary program
Presenter: Ana Monteiro
Session: Poster Display session 1
Resources:
Abstract
5340 - Quantitative imaging and characterization of collagen patterns in high grade serous ovarian carcinoma (HGSOC)
Presenter: Ruby Huang
Session: Poster Display session 1
Resources:
Abstract
4209 - Semiquantitative assessment of vimentin expression in prostate cancer (PC)
Presenter: Marina Puchinskaya
Session: Poster Display session 1
Resources:
Abstract
3309 - Heat Shock Protein 90 chaperones and Protein Kinase D3 regulates androgen-independent prostate cancer development
Presenter: Attila Varga
Session: Poster Display session 1
Resources:
Abstract