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A and B show the range of alveolar septal thickening from mild to moderate due to increased fibroblastic stroma (red arrow) and mononuclear inflammatory cell infiltration. C shows multiple areas of intra-alveolar fibrin leakage with mononuclear infiltration (blue arrows) and pneumocyte type II hyperplasia with reactive atypia (red arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)
Source publication
Background
Paclitaxel is a chemotherapeutic drug widely used in breast cancer treatment. While common side effects are possible, paclitaxel-induced pneumonitis is rare, with an estimated incidence of 1%–5% and a high mortality rate.
Case presentation
A 57-year-old Thai woman diagnosed with stage II right breast cancer. She received adjuvant chemot...
Context in source publication
Context 1
... hyperplasia with reactive changes was also evident. Bronchial tissue exhibited mild lymphocyte infiltration with no neutrophil infiltration. No granulomas, foamy material, fungi, or viral inclusions were detected. These pathological observations consistently aligned with moderate subacute lung injury, morphologically congruent with AFOP (Fig. ...
Citations
... Systemic chemotherapy with anthracyclines and taxanes is the most common first-line treatment modality [3]. However, anticancer drug resistance, off-target toxicity, and complications, including pneumonia with severe inflammation, are major obstacles to the development of cancer chemotherapy regimens [4][5][6]. Although the possible molecular mechanisms of TNBC tumor growth, metastasis, and therapy have been increasingly revealed, their clinical application is still limited. ...
Background
The Golgi apparatus is widely considered a secretory center and a hub for different signaling pathways. Abnormalities in Golgi dynamics can perturb the tumor microenvironment and influence cell migration. Therefore, unraveling the regulatory network of the Golgi and searching for pharmacological targets would facilitate the development of novel anticancer therapies. Previously, we reported an unconventional role for the Golgi tethering factor golgin-97 in inhibiting breast cell motility, and its downregulation was associated with poor patient prognosis. However, the specific role and regulatory mechanism of golgin-97 in cancer progression in vivo remain unclear.
Methods
We integrated genetic knockout (KO) of golgin-97, animal models (zebrafish and xenograft mice), multi-omics analysis (next-generation sequencing and proteomics), bioinformatics analysis, and kinase inhibitor treatment to evaluate the effects of golgin-97 KO in triple-negative breast cancer cells. Gene knockdown and kinase inhibitor treatment followed by qRT‒PCR, Western blotting, cell viability, migration, and cytotoxicity assays were performed to elucidate the mechanisms of golgin-97 KO-mediated cancer invasion. A xenograft mouse model was used to investigate cancer progression and drug therapy.
Results
We demonstrated that golgin-97 KO promoted breast cell metastasis in zebrafish and xenograft mouse models. Multi-omics analysis revealed that the Wnt signaling pathway, MAPK kinase cascades, and inflammatory cytokines are involved in golgin-97 KO-induced breast cancer progression. Targeting the ERK1/2 and p38 MAPK pathways effectively attenuated golgin-97-induced cancer cell migration, reduced the expression of inflammatory mediators, and enhanced the chemotherapeutic effect of paclitaxel in vitro and in vivo. Specifically, compared with the paclitaxel regimen, the combination of ERK1/2 and p38 MAPK inhibitors significantly prevented lung metastasis and lung injury. We further demonstrated that hypoxia is a physiological condition that reduces golgin-97 expression in cancer, revealing a novel and potential feedback loop between ERK/MAPK signaling and golgin-97.
Conclusion
Our results collectively support a novel regulatory role of golgin-97 in ERK/MAPK signaling and the tumor microenvironment, possibly providing new insights for anti-breast cancer drug development.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12964-024-02010-0.
