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New Function Annotation of PROSER2 in Pancreatic Ductal Adenocarcinoma
Yu-Sun Lee1,2, Jieun Im1, Yeji Yang3,4
1Division of Convergence Technology, Research Institute of National Cancer Center, Goyang 10408, Republic of Korea.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis due to the absence of diagnostic markers and molecular targets. Here, we took an unconventional approach to identify new molecular targets for pancreatic cancer. We chose uncharacterized protein evidence level 1 without function annotation from extensive proteomic research on pancreatic cancer and focused on proline and serine-rich 2 (PROSER2), which ranked high in the cell membrane and cytoplasm. In our study using cell lines and patient-derived orthotopic xenograft cells, PROSER2 exhibited a higher expression in cells derived from primary tumors than in those from metastatic tissues. PROSER2 was localized in the cell membrane and cytosol by immunocytochemistry. PROSER2 overexpression significantly reduced the metastatic ability of cancer cells, whereas its suppression had the opposite effect. Proteomic analysis revealed that PROSER2 interacts with STK25 and PDCD10, and their binding was confirmed by immunoprecipitation and immunocytochemistry. STK25 knockdown enhanced metastasis by decreasing p-AMPK levels, whereas PROSER2-overexpressing cells increased the level of p-AMPK, indicating that PROSER2 suppresses invasion via the AMPK pathway by interacting with STK25. This is the first demonstration of the novel role of PROSER2 in antagonizing tumor progression via the STK25-AMPK pathway in PDAC. LC-MS/MS data are available at MassIVE (MSV000092953) and ProteomeXchange (PXD045646).
Insights
Researchers identified Proline and Serine-Rich 2 (PROSER2) as a novel target for pancreatic cancer. PROSER2 suppresses tumor metastasis by interacting with STK25 and activating the AMPK pathway, offering new therapeutic avenues.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) lacks effective diagnostic markers and molecular targets, contributing to its poor prognosis.
- Uncharacterized proteins from proteomic research present opportunities for identifying novel therapeutic targets.
Purpose of the Study:
- To identify and characterize novel molecular targets for pancreatic cancer.
- To investigate the role of proline and serine-rich 2 (PROSER2) in PDAC progression and metastasis.
Main Methods:
- Proteomic analysis of pancreatic cancer tissues and cell lines.
- Immunocytochemistry and immunoprecipitation to confirm protein interactions.
- Functional assays using cell lines and patient-derived xenografts to assess metastatic ability.
- Western blotting to analyze signaling pathway activation (AMPK).
Main Results:
- PROSER2 expression was higher in primary tumor cells compared to metastatic cells.
- PROSER2 overexpression reduced cancer cell metastasis, while suppression increased it.
- PROSER2 interacts with STK25 and PDCD10.
- PROSER2 suppresses invasion via the STK25-AMPK pathway by increasing p-AMPK levels.
Conclusions:
- PROSER2 plays a novel role in antagonizing tumor progression in PDAC.
- The STK25-AMPK pathway is a key mechanism through which PROSER2 exerts its anti-metastatic effects.
- PROSER2 represents a potential new therapeutic target for pancreatic cancer.
