Alfredo Smiriglia

Targeting the LIPH-CD36 axis potentiates CDK4/6 inhibition in ER+ breast cancer

Andrea Morandi, Nicla Lorito, Elisabetta Romano, Alfredo Smiriglia et autres

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Under pressure: peroxisomes in cancer therapy resistance

Nicla Lorito, Francesca Bonechi, Elisabetta Romano, Alfredo Smiriglia et autres

Therapy resistance is a major obstacle to durable clinical responses. While genetic alterations and signalling rewiring are primary drivers of resistance, metabolic adaptation, which is closely intertwined with these processes, enables tumour persistence under therapeutic pressure and directly contributes to resistance. Peroxisomes …

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Cell Cycle Control of Nuclear Metabolism Couples Phosphatidylinositol Signaling to Histone Methylation

Antoni Gañez Zapater, Savvas Kourtis, Camilla Reiter Elbæk, Lorena Espinar et autres

Progression through the cell cycle requires coordinated regulation of transcription, chromatin state, and cellular metabolism. While metabolic enzymes are known to localize the nucleus and influence chromatin states, how nuclear metabolism itself oscillates during the cell cycle remains unexplored. Here, we combine …

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Lead induces cell-autonomous proliferation and metabolic reprogramming of hepatocytes

Marina Serra, Alfredo Smiriglia, Cristina Migliore, Andrea Caddeo et autres

Reprogramming of energy metabolism is widely recognized as a hallmark of cancer cells. However, recent evidence indicates that metabolic reprogramming also occurs in vivo in differentiated rat hepatocytes following administration of the primary mitogen lead nitrate (LN). It remains unclear whether this …

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ESR1 -Activating Mutations Confer Metabolic Vulnerabilities in ER+ Breast Cancer

Francesca Bonechi, Marina Bacci, Nicla Lorito, Alfredo Smiriglia et autres

Endocrine therapy (ET) is the standard of care for estrogen receptor (ER)-positive breast cancer. Point mutations in the ligand-binding domain of the gene encoding the estrogen receptor (ESR1) are rare in naïve ER+ breast cancer while becoming common in the ET-resistant setting. …

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CD44 and SLC1A2 are commonly regulated but do not form a fusion transcript in ER+ breast cancer

Francesca Bonechi, Marina Bacci, Nicla Lorito, Alfredo Smiriglia et autres

Endocrine therapy (ET) is essential for managing ER+ HER2- breast cancer; however, resistance remains a significant clinical challenge. This study investigated whether CD44-SLC1A2 gene fusions, reported in gastrointestinal malignancies, contribute to ET resistance mechanisms in breast cancer. Although no CD44-SLC1A2 fusions were …

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Estrogen-dependent activation of TRX2 reverses oxidative stress and metabolic dysfunction associated with steatotic disease

Alfredo Smiriglia, Nicla Lorito, Marina Bacci, Angela Subbiani et autres

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of hepatic disorders, ranging from simple steatosis to steatohepatitis, with the most severe outcomes including cirrhosis, liver failure, and hepatocellular carcinoma. Notably, MASLD prevalence is lower in premenopausal women than in men, suggesting …

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FADS1/2 control lipid metabolism and ferroptosis susceptibility in triple-negative breast cancer

Nicla Lorito, Angela Subbiani, Alfredo Smiriglia, Marina Bacci et autres

Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of …

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Estrogen-dependent TRX2 activation reverts oxidative stress and metabolic dysfunction associated to steatotic disease

Andrea Morandi, Alfredo Smiriglia, Nicla Lorito, Marina Bacci et autres

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Acetyl-CoA carboxylase 1 controls a lipid droplet–peroxisome axis and is a vulnerability of endocrine-resistant ER + breast cancer

Marina Bacci, Nicla Lorito, Alfredo Smiriglia, Angela Subbiani et autres

Targeting aromatase deprives ER + breast cancers of estrogens and is an effective therapeutic approach for these tumors. However, drug resistance is an unmet clinical need. Lipidomic analysis of long-term estrogen-deprived (LTED) ER + breast cancer cells, a model of aromatase inhibitor …

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Sex difference in liver diseases: How preclinical models help to dissect the sex-related mechanisms sustaining NAFLD and hepatocellular carcinoma

Alfredo Smiriglia, Nicla Lorito, Marina Serra, Andrea Perra et autres

Summary Only a few preclinical findings are confirmed in the clinic, posing a critical issue for clinical development. Therefore, identifying the best preclinical models can help to dissect molecular and mechanistic insights into liver disease pathogenesis while being clinically relevant. In this …

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FADS1/2-mediated lipid metabolic reprogramming drives ferroptosis sensitivity in triple-negative breast cancer

Nicla Lorito, Angela Subbiani, Alfredo Smiriglia, Marina Bacci et autres

Abstract Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type …

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