FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer

Qiu, Li; Hu, Linfei; Wang, Huijuan; Li, Jinling; Ruan, Xianhui; Sun, Bingjie; Jiang, Zhi; Zheng, Xiangqian; Gu, Lin; Gao, Ming; Kong, Ping; Zhang, Jun

doi:10.1038/s41419-020-03052-1

Cited by 7 publications

(7 citation statements)

References 44 publications

(52 reference statements)

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“…It would have also been more informative if we had collected information on other biochemical and biological parameters of cellular metabolism. 32,33 Based on our results, we have highlighted the association between treatment-related toxicities and malnutrition, and the relevance of malnutrition on patient-reported QoL. As a next step, we hypothesized that active and timely nutritional intervention could mitigate the extent of malnutrition and reverse some of the impact on QoL.…”

Section: Discussionmentioning

confidence: 73%

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Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study

Miao

Wang

Ong

et al. 2023

J cachexia sarcopenia muscle

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Background Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). This intensive treatment regimen increases acute toxicities, which could negatively impact patients' nutritional status. We conducted this prospective, multicentre trial to investigate the effects of IC and CCRT on nutritional status in LA‐NPC patients, so as to provide evidence for further study of nutritional intervention, which was registered in http://ClinicalTrials.gov (NCT02575547). Methods Patients with biopsy‐proven NPC and planned for IC + CCRT were recruited. IC entailed two cycles of 3‐weekly docetaxel 75 mg/m2 and cisplatin 75 mg/m2; CCRT entailed two to three cycles of 3‐weekly cisplatin 100 mg/m2 depending on the duration of radiotherapy. Nutritional status and quality of life (QoL) were assessed pre‐IC, post‐cycles one and two of IC, W4 and W7 of CCRT. Primary endpoint was the cumulative proportion of ≥ 5.0% weight loss (WL5.0) by the end of treatment (W7‐CCRT). Secondary endpoints included body mass index, NRS2002 and PG‐SGA scores, QoL, hypoalbuminaemia, treatment compliance, acute and late toxicities and survivals. The associations between primary and secondary endpoints were also evaluated. Results One hundred and seventy‐one patients were enrolled. Median follow‐up was 67.4 (IQR: 64.1–71.2) months. 97.7% (167/171) patients completed two cycles of IC, and 87.7% (150/171) completed at least two cycles of concurrent chemotherapy; all, except one patient (0.6%), completed IMRT. WL was minimal during IC (median of 0.0%), but increased sharply at W4‐CCRT (median of 4.0% [IQR: 0.0–7.0%]) and peaked at W7‐CCRT (median of 8.5% [IQR: 4.1–11.7%]). 71.9% (123/171) of patients recorded a WL5.0 by W7‐CCRT, which was associated with a higher malnutrition risk (NRS2002 ≥ 3 points: 87.7% [WL ≥ 5.0%] vs 58.7% [WL < 5.0%], P < 0.001) and requirement of nutritional intervention (PG‐SGA ≥ 9 points: 82.0% [WL ≥ 5.0%] vs 66.7% [WL < 5.0%], P = 0.038). The median %WL at W7‐CCRT was higher in patients who suffered from ≥ G2 mucositis (9.0% vs 6.6%, P = 0.025) and xerostomia (9.1% vs 6.3%, P = 0.003). Besides, patients with cumulative WL5.0 also reported a higher detriment on QoL at W7‐CCRT compared with patients without, with a difference of −8.3 points (95% CI [−15.1, −1.4], P = 0.019). Conclusions We observed a high prevalence of WL among LA‐NPC patients who were treated with IC + CCRT, which peaked during CCRT, and had a detriment on patients' QoL. Our data support the need to monitor patient's nutritional status during the later phase of treatment with IC + CCRT and inform on nutritional intervention strategies.

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Section: Discussionmentioning

confidence: 73%

“…Next, we acknowledge that WL is a crude surrogate of malnutrition, and other indicators such as sarcopenia (measured on scans) would be more representative of a patient's nutritional status. It would have also been more informative if we had collected information on other biochemical and biological parameters of cellular metabolism 32,33 …”

Section: Discussionmentioning

confidence: 99%

Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study

Miao

Wang

Ong

et al. 2023

J cachexia sarcopenia muscle

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“…A link between ERβ and autophagy in LC has been suggested by Qiu and co-workers in a recent study [121]. They observed that fragile-site associated tumor suppressor (FATS), a novel oncogene involved in LC, was significantly downregulated in NSCLC tissues compared with adjacent normal tissues and was associated with the survival of NSCLC patients.…”

Section: Lung Carcinomamentioning

confidence: 84%

“…FATS was shown to function as a suppressor of polyamine biosynthesis by inhibiting ornithine decarboxylase (ODC) at the protein and mRNA levels, and this mechanism was dependent on ERβ. In fact, FATS binds to ERβ and translocates to the cytosol, leading to ODC degradation [121].…”

Section: Lung Carcinomamentioning

confidence: 99%

The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy

Matarrese

Mattia

Pagano

et al. 2021

Cancers

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The interplay between cancer cells and the tumor microenvironment (TME) has a fundamental role in tumor progression and response to therapy. The plethora of components constituting the TME, such as stroma, fibroblasts, endothelial and immune cells, as well as macromolecules, e.g., hormones and cytokines, and epigenetic factors, such as microRNAs, can modulate the survival or death of cancer cells. Actually, the TME can stimulate the genetically regulated programs that the cell puts in place under stress: apoptosis or, of interest here, autophagy. However, the implication of autophagy in tumor growth appears still undefined. Autophagy mainly represents a cyto-protective mechanism that allows cell survival but, in certain circumstances, also leads to the blocking of cell cycle progression, possibly leading to cell death. Since significant sex/gender differences in the incidence, progression and response to cancer therapy have been widely described in the literature, in this review, we analyzed the roles played by key components of the TME, e.g., estrogen and microRNAs, on autophagy regulation from a sex/gender-based perspective. We focused our attention on four paradigmatic and different forms of cancers—colon cancer, melanoma, lymphoma, and lung cancer—concluding that sex-specific differences may exert a significant impact on TME/cancer interaction and, thus, tumor growth.

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“…While the role of rare fragile sites in tumors remains unclear, CFS is consistent for many tumor genome mutations, and they are closely related to the occurrence and development of tumors (9). The introns and expression regulatory regions of fragile-site associated tumor suppressor (FATS) gene are rich in AT repeat sequences and have characteristics of typical fragile locus genes (10). FATS is a tumor suppressor gene associated with DNA damage-induced tumors.…”

Section: Introductionmentioning

confidence: 99%

Plasma exosome-derived fragile-site associated tumor suppressor is a powerful predictor of prognosis in patients with ovarian cancer

Chen

Zhang

et al. 2021

Bosn J of Basic Med Sci

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Objective: To investigate the levels of plasma exosome-derived fragile-site associated tumor suppressor (FATS) and evaluate its predictive ability in ovarian cancer (OC) patients. Patients and Methods: Exosome-rich fractions were isolated from the plasma of enrolled 90 patients with OC. The levels of plasma exosome-derived FATS were detected with ELISA. Results: The levels of exosome-derived FATS in OC patient were significantly lower than in healthy controls (P < 0.001). The levels of plasma exosome-derived FATS were obviously higher in OC patients with low grade (1/2), FIGO stages I/II than high grade (3/4), stages III/ IV disease (P = 0.003; P < 0.001). The levels of plasma exosome-derived FATS were significantly higher in OC patients with no lymph node metastasis, no ascites than those with lymph node metastasis, ascites (both P < 0.001). The levels of plasma exosome-derived FATS were obviously higher in OC patients with CA-125 less than 35U/ml than more than 35U/ml (P < 0.001). Among all enrolled OC patients, both 5-DFS and 5-OS were shorter in patients who had low plasma exosome-derived FATS levels than that high levels (both P < 0.001). The AUROC of plasma exosome-derived FATS were 0.85(95% CI: 0.76-0.91) for 5-DFS, 0.91(95% CI: 0.83-0.96) for 5-OS prediction in patients with OC, respectively. Conclusions: Plasma exosome-derived FATS levels in OC patient were significantly down-regulated. Low levels of plasma exosome-derived FATS had close relationship with FIGO stages I/II, low grade, ascites, higher levels of CA-125, lymph node metastasis and prognosis of OC patients. Our findings may provide a new strategy in treating OC.

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FATS regulates polyamine biosynthesis by promoting ODC degradation in an ERβ-dependent manner in non-small-cell lung cancer

Cited by 7 publications

References 44 publications

Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study

Effects of induction chemotherapy on nutrition status in locally advanced nasopharyngeal carcinoma: a multicentre prospective study

The Sex-Related Interplay between TME and Cancer: On the Critical Role of Estrogen, MicroRNAs and Autophagy

Plasma exosome-derived fragile-site associated tumor suppressor is a powerful predictor of prognosis in patients with ovarian cancer

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