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Published on: March 27, 2020
Protein tyrosine phosphatase PTPL1 suppresses lung cancer through Src/ERK/YAP1 signaling
Jing Wang1, Shuanghui Li1, Xiujuan Zhang1
1Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Background:
To reveal the function of protein tyrosine phosphatase-L1 (PTPL1) in lung adenocarcinoma.
Methods:
Lung cancer cell lines were transfected with short hairpin RNA against PTPL1 (shPTPL1 group) or negative control (shmock group). Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to verify the transfection efficacy. Cell proliferation was analyzed by ethynyldeoxyuridine (EdU), Cell counting kit 8 (CCK8), and colony formation assay after PTPL1 or PTPL1 and yes-associated protein (YAP1) knockdown. The effect of PTPL1 on tumor growth was examined in a xenograft lung cancer model.
Results:
PTPL1 was downregulated in various types of lung cancer cell lines. The EdU, CCK8, colony formation assays and investigation using a xenograft lung cancer model indicated that PTPL1 knockdown increased the proliferation of lung cancer cells. Mechanistically, PTPL1 knockdown induced the activation of the Proto-oncogene tyrosine-protein kinase SRC (Src)/Extracellular regulated MAP kinase (ERK) pathway and thereby promoted yes-associated protein (YAP1) nuclear translocation and activation.
Conclusions:
In our study, PTPL1 played a crucial suppressive role in the pathogenesis of lung cancer potentially through counteracting the Src/ERK/YAP1 pathway.
Insights
Protein tyrosine phosphatase-L1 (PTPL1) suppresses lung cancer growth. Downregulating PTPL1 promotes cancer cell proliferation by activating the Src/ERK/YAP1 pathway, highlighting PTPL1 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Lung adenocarcinoma is a major global health concern.
- Understanding the molecular mechanisms driving lung cancer progression is critical for developing effective treatments.
Purpose of the Study:
- To investigate the functional role of protein tyrosine phosphatase-L1 (PTPL1) in lung adenocarcinoma.
- To elucidate the molecular pathways regulated by PTPL1 in lung cancer.
Main Methods:
- Utilized short hairpin RNA (shRNA) to knockdown PTPL1 in lung cancer cell lines.
- Assessed cell proliferation using EdU, CCK8, and colony formation assays.
- Examined tumor growth in a xenograft mouse model and analyzed molecular signaling pathways (Src/ERK/YAP1).
Main Results:
- PTPL1 expression was found to be downregulated in lung cancer cell lines.
- Knockdown of PTPL1 significantly increased lung cancer cell proliferation and tumor growth.
- PTPL1 downregulation activated the Src/ERK pathway, leading to YAP1 nuclear translocation and activation.
Conclusions:
- PTPL1 acts as a tumor suppressor in lung adenocarcinoma.
- PTPL1 counteracts the Src/ERK/YAP1 signaling pathway, inhibiting lung cancer cell proliferation and growth.
- PTPL1 represents a potential therapeutic target for lung cancer treatment.
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