Abstract 4273
Background
Lung cancer is the main cause of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) is one of the major molecular mechanisms inducing tumor invasion and metastasis. Paired-related homeobox 1 (Prrx1) is a newly found EMT-inducing transcription factor. The prognostic value of Prrx1 in lung cancer has not been well demonstrated.
Methods
H1299-Prrx1 cell lines were generated by transfecting the pcDNA3.1-Prrx1 plasmid into H1299 cells. The H1299-Prrx1-Twisti cell lines were generated by transfecting the pSUPER-Twisti plasmid into H1299-Prrx1 cells. Immunofluorescence staining was done to demonstrate expression of E-cadherin and vimentin in these cells. Soft agar clonogenicity assay was done in these cell lines to demonstrate anchorage-independent growth. Cell migration and invasiveness assay were done in these cells to demonstrate their invasion and migration ability. In vivo tail vein metastasis assay was done to demonstrate the ability of Prrx1 overexpression in metastasis in vivo. Immunohistochemistry analysis of Prrx1 expression was done in 110 specimens of lung cancer patients.
Results
Prrx1 overexpression increased transformation activity, induced EMT and increased migration/invasiveness of H1299 cells. Prrx1 overexpression also increased metastatic ability in vivo. Prrx1 overexpression upregulated the expression of Twist and its downstream target matrix metalloproteinase 1 (MMP1). EMT phenotypes, increased migration/invasiveness of H1299-Prrx1 cells, and increase MMP1 expression were reversed by siRNA-mediated repression of Twist expression or a phosphatidylinositol (PI) 3-kinase inhibitor. Prrx1 overexpression predicted lower recurrence-free survival in patients with lung adenocarcinoma.
Conclusions
Prrx1 overexpression induces EMT through upregulation of PI 3-kinase/Akt/Twist/MMP1 axis. Prrx1 overexpression also predicts recurrence in lung cancer patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
920 - Efficacy of intravenous (IV) NEPA, a fixed NK1/5-HT3 receptor antagonist (RA) combination, for prevention of CINV following cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy (CT)
Presenter: Lee Schwartzberg
Session: Poster Display session 1
Resources:
Abstract
5146 - Efficacy of olanzapine combination in prevention of nausea & vomiting in highly emetogenic chemotherapy
Presenter: Smitha Saldanha
Session: Poster Display session 1
Resources:
Abstract
1947 - Patient-reported outcome data during real-world use of NEPA for prevention of chemotherapy-induced nausea and vomiting in high-risk platin-receiving patients - A prospective multicenter trial
Presenter: Meinolf Karthaus
Session: Poster Display session 1
Resources:
Abstract
6163 - A study evaluating steroid induced metabolic syndrome after antiemetic dexamethasone therapy in patients received high emetic risk chemotherapy
Presenter: Hee Jun Kim
Session: Poster Display session 1
Resources:
Abstract
2154 - High incidence of nausea during initial and repeated courses if intravenous chemotherapy in patients receiving guideline consistent antiemetic prophylaxis - a prospective, observational, real world study.
Presenter: Teresa Smit
Session: Poster Display session 1
Resources:
Abstract
1637 - "Randomised controlled trial of Scalp Cooling (SC) for the prevention of Chemotherapy Induced Alopecia (CIA)”
Presenter: Jyoti Bajpai
Session: Poster Display session 1
Resources:
Abstract
5351 - Performance of the ‘4S rule’ to predict short-term outcomes in cancer outpatients with unsuspected pulmonary embolism.
Presenter: David Pesántez Coronel
Session: Poster Display session 1
Resources:
Abstract
1189 - Prevalence of venous thromboembolism based on intensive screening for patients with advanced solid tumor in prospective observational study
Presenter: Shota Omori
Session: Poster Display session 1
Resources:
Abstract
4340 - Short-term outcomes of cancer patients with pulmonary embolism according to the setting (hospital-acquired vs. outpatient) at diagnosis.
Presenter: Diego Muñoz Guglielmetti
Session: Poster Display session 1
Resources:
Abstract
4658 - Patient-reported outcomes associated with switching to rivaroxaban for the treatment of venous thromboembolism (VTE) in patients with active cancer
Presenter: Alexander Cohen
Session: Poster Display session 1
Resources:
Abstract