ArticleMolecular cancer research : MCR2025
Novel Metastasis Suppressor PI3KC2β Is Mediated by mTORC1 Signaling in Breast Cancer.
Article in Molecular cancer research : MCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
HER2 amplification or mutation accounts for 25% of patients with breast cancer that can advance to metastatic disease. Therefore, it is important to identify novel genes that mediate metastasis in HER2+ breast cancer. In this study, we describe a new metastatic suppressor gene, class II phosphatidylinositol 3-kinase β (Pi3kc2β), through in vivo CRISPR-Cas9 library screening of a custom-designed library targeting genes implicated in autophagy using murine HER2+ breast cancer (N418) cells. We further showed that PI3KC2β knockout N418 cells increased their migration and invasion in vitro and lung metastasis in both spontaneous and experimental metastasis assays in vivo. Analysis of databases and tissue samples from patients with breast cancer correlated lower expression of PI3KC2β with decreased metastasis, overall survival, and relapse-free survival. Further, PI3KC2β deletion induced the activation of mTORC1 signaling, independent of affecting its kinase activity. Mechanistically, we found that PI3KC2β forms a complex with intersectin 1 (ITSN1) and raptor that could be decreasing the stability of raptor, and deletion of either PI3KC2β or ITSN1 led to increased raptor levels and mTORC1 signaling. Lastly, rapamycin treatment reduced the migration and invasion of PI3KC2β knockout tumor cells in vitro and their lung metastasis in vivo, supporting an important role of the mTORC1 pathway. Together, our results identify PI3KC2β as a suppressor of HER2+ breast cancer metastasis by negatively regulating mTORC1 signaling by affecting its complex formation with ITSN1 and raptor. IMPLICATIONS: Our findings revealed PI3KC2β as a new metastasis suppressor for HER2+ breast cancer, which might serve as a potential diagnostic and therapeutic target for the disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.