401 Loss of LKB1/STK11 expression is an early event in prostate cancer development and predicts therapeutic response to p38α inhibitor

Grossi, Valentina; Lucarelli, Giuseppe; Matrone, Antonio; Forte, Giusi Irma; Germani, Alessandra; Rutigliano, Monica; Stella, Alexander; Bagnulo, Rosanna; Loconte, Daria Carmela; Galleggiante, Vanessa; Sanguedolce, Francesca; Cagiano, Simona; Bufo, Pantaleo; Trabucco, S.; Ditonno, Pasquale; Battaglia, Michele; Resta, Nicoletta; Simone, Cristiano

doi:10.1016/s1569-9056(15)60395-5

Cited by 2 publications

(1 citation statement)

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“…LKB1 is a type of tumor suppressor gene and relatively highly expressed in esophageal tissue, which directly activates AMPK catalytic subunit PRKAA1, PRKAA2, and thereby regulates other downstream processes. The protein level of LKB1 decreased throughout prostate carcinogenesis, with a significant reduction already evident in high-grade prostate intraepithelial neoplasia lesions and a complete loss in adenocarcinomas (17). Studies demonstrated that ∼30% of sporadic breast cancer samples expressed low levels of LKB1, yet overexpression of LKB1 protein was associated with a decrease in tumor micro vessel density (18).…”

Section: Discussionmentioning

confidence: 99%

Angustoline Inhibited Esophageal Tumors Through Regulating LKB1/AMPK/ELAVL1/LPACT2 Pathway and Phospholipid Remodeling

Zhang

et al. 2020

Front. Oncol.

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Esophageal cancer is a type of gastrointestinal carcinoma and is among the 10 most common causes of cancer death worldwide. However, the specific mechanism and the biomarkers in the proliferation and metastasis of esophageal tumors are still unclear. Therefore, the development of several natural products which could inhibit esophageal tumors deserve attention. In the present study, different sources of cancer cells were used to select the sensitive cell line (esophageal cancer cell KYSE450) and the proper dose of angustoline, which were utilized in the following cell viability, migration and invasion assays. Then the lipidomic detection of clinical samples (tissue and blood plasma) from esophageal cancer patients was performed, to screen out the specific phospholipid metabolites [PC (16:0/18:1) and LPC (16:0)]. Considering lysophosphatidylcholine acyltransferase 2 (LPCAT2) was tightly relative with phospholipids conversion, serine/threonine-protein kinase 11 (LKB1), 5 ′-monophosphate (AMP)-activated protein kinase (AMPK) and embryonic lethal, and abnormal vision, drosophila-like 1 (ELAVL1) were investigated, to evaluate their expression levels in esophageal tumor tissue and KYSE450 cells. Additionally, KYSE450 tumor bearing mouse model was constructed, the role of angustoline in inhibiting esophageal tumors through regulating LKB1/AMPK/ELAVL1/LPCAT2 pathway was validated, and found that the conversion from LPC (16:0) to PC (16:0/18:1) was blocked by angustoline in some degree. The above results for the first time proved that angustoline suppressed esophageal tumors through activating LKB1/AMPK and inhibiting ELAVL1/LPCAT2, which consequently blocked phospholipid remodeling from LPC (16:0) to PC (16:0/18:1).

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Section: Discussionmentioning

confidence: 99%

Angustoline Inhibited Esophageal Tumors Through Regulating LKB1/AMPK/ELAVL1/LPACT2 Pathway and Phospholipid Remodeling

Zhang

et al. 2020

Front. Oncol.

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Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer

Lucarelli

Rutigliano

Galleggiante

et al. 2015

Expert Review of Molecular Diagnostics

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Metabolomic profiling offers a powerful methodology for understanding the perturbations of biochemical systems occurring during a disease process. During neoplastic transformation, prostate cells undergo metabolic reprogramming to satisfy the demands of growth and proliferation. An early event in prostate cell transformation is the loss of capacity to accumulate zinc. This change is associated with a higher energy efficiency and increased lipid biosynthesis for cellular proliferation, membrane formation and cell signaling. Moreover, recent studies have shown that sarcosine, an N-methyl derivative of glycine, was significantly increased during disease progression from normal to localized to metastatic prostate cancer. Mapping the metabolomic profiles to their respective biochemical pathways showed an upregulation of androgen-induced protein synthesis, an increased amino acid metabolism and a perturbation of nitrogen breakdown pathways, along with high total choline-containing compounds and phosphocholine levels. In this review, the role of emerging biomarkers is summarized, based on the current understanding of the prostate cancer metabolome.

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401 Loss of LKB1/STK11 expression is an early event in prostate cancer development and predicts therapeutic response to p38α inhibitor

Cited by 2 publications

References 0 publications

Angustoline Inhibited Esophageal Tumors Through Regulating LKB1/AMPK/ELAVL1/LPACT2 Pathway and Phospholipid Remodeling

Angustoline Inhibited Esophageal Tumors Through Regulating LKB1/AMPK/ELAVL1/LPACT2 Pathway and Phospholipid Remodeling

Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer

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