Abstract 3156
Background
LAPTM5 (lysosomal-associated protein transmembrane 5) is a protein that is preferentially expressed in immune cells, and it interacts with the Nedd4 family of ubiquitin ligases. Recent studies in T and B cells identified LAPTM5 as a negative regulator of T and B cell receptor levels at the plasma membrane, but a positive modulator of inflammatory signaling pathways and hence cytokine secretion in macrophages. However, the expression and function of LAPTM5 in ovarian cancer remains undefined.
Methods
LAPTM5 expression in ovarian cancer, benign and normal ovarian tissues was examined by immunohistochemistry. The LAPTM5 mRNA and protein level of OV cells were detected by Q-PCR and Western blotting respectively. Cell apoptosis, migration and invasion changes were observed through high-content screening. The proteins expression involved in epithelial-mesenchymal transition (EMT) and TGF-β mediated signaling pathways was verified by Werstern blotting and immunofluorescence. The role of LAPTM5 on tumorigenesis in vivo was detected by the xenograft model.
Results
Our study showed that in human OV cell lines and tissues, LAPTM5 were significantly induced at both mRNA and protein levels. Furthermore, an OV cell model with downregulated LAPTM5 were established, revealing a significantly alteration of apoptosis. Moreover, analysis of the changes of migration and invasion, showed significant reduced LAPTM5 suppressed cell metastasis. Proteins involved in EMT were strongly altered, which plays a central role in cell metastasis. In addition, phosphorylated ERK1/2, p38 and JNK, key members of mitogen-activated protein kinase (MAPK) family, and phosphorylated Smad2 and Smad3 of Smad signaling pathways mediated by TGF-β regulating OV cells EMT, were strongly decreased. And, LAPTM5 knockdown also inhibited tumorigenesis in xenograft model.
Conclusions
Taken together, our results suggested that LAPTM 5 acts as a positive modulator of MAPK and TGFβ/Smad signaling pathways mediated by TGFβ in OV cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Beijing Obstetrics and Gynecology Hospital, Capital Medical University.
Funding
The National Natural Science Foundation of China (grants 81672838), Beijing Municipal Science & Technology Commission (No. Z181100001718193).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3158 - Tobacco Retail Access and Tobacco Cessation Among Head and Neck Cancer (HNC) Survivors
Presenter: Lawson Eng
Session: Poster Display session 1
Resources:
Abstract
5511 - ASSERT: A Prospective, Observational Study Measuring Sodium Improvement and Outcomes in Patients Treated for Moderate to Severe Hyponatremia Secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in Italy (Lung Cancer Cohort)
Presenter: Rossana Berardi
Session: Poster Display session 1
Resources:
Abstract
3821 - Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: A systematic review and meta-analysis.
Presenter: Benedetta Bonardi
Session: Poster Display session 1
Resources:
Abstract
2168 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy
Presenter: Tineke Vandenbroucke
Session: Poster Display session 1
Resources:
Abstract
5855 - Update of the registry of young women with cancer by the International Network of Cancer, Infertility and Pregnancy
Presenter: Charlotte Maggen
Session: Poster Display session 1
Resources:
Abstract
5156 - Erectile dysfunction in patients with metastatic renal cell carcinoma
Presenter: Ilya Tsimafeyeu
Session: Poster Display session 1
Resources:
Abstract
4992 - Exercise level, interest and preferences in cancer patients.
Presenter: Alice Avancini
Session: Poster Display session 1
Resources:
Abstract
3427 - Filling the Gaps in Informed Consent for Advanced Cancer Patients considering Phase 1 Oncology Trials - an in-depth Qualitative Study of Key Stakeholders at a large United Kingdom Phase 1 unit
Presenter: Abhijit Pal
Session: Poster Display session 1
Resources:
Abstract
3537 - Breast Cancer Patients’ Quality of Life: Real World Data
Presenter: Thanos Kosmidis
Session: Poster Display session 1
Resources:
Abstract
4761 - High-sensitivity troponin as a cardiotoxicity biomarker in breast cancer treatment
Presenter: Joana Simões
Session: Poster Display session 1
Resources:
Abstract