BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism

Luo, Lixiang; Sun, Wenjing; Zhu, Weijian; Li, Shuhan; Zhang, Wenqi; Xu, Xiaohui; Fang, Daoquan; Grahn, Tan Hooi Min; Jiang, Lei; Zheng, Yijing

doi:10.1038/s41419-021-03456-7

Cited by 55 publications

(37 citation statements)

References 36 publications

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“…For example, the kinesin superfamily (KIF) members KIF14 and KIF23 have been shown to promote cisplatin-resistance in HCC (Cheng et al, 2020). Branched-chain amino acid transaminase 1 (BCAT1) (Luo et al, 2021). In addition, many long noncoding RNAs, circular RNAs, and micro RNAs were also involved in chemoresistance to cisplatin in hepatocellular carcinoma (Ding et al, 2019;Luo et al, 2019;Pratama et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

Zhang

Yang

Yao

et al. 2021

Cell Biology International

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Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8 + T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

Zhang

Yang

Yao

et al. 2021

Cell Biology International

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“…In HCC, BCAT1 plays a pathogenic role by promoting cell proliferation and chemoresistance ( 33 ). BCAT1 regulates mTOR-mediated autophagy via branched-chain amino acid metabolism, thus reducing the sensitivity of cancer cells to cisplatin ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of an Invasion-Related 3-Gene Signature and Its Validation as a Prognostic Model for Pancreatic Cancer

Wang

Zhang

et al. 2021

Front. Oncol.

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BackgroundPancreatic adenocarcinoma (PAAD) is a malignant tumor of the digestive system that is associated with a poor prognosis in patients owing to its rapid progression and high invasiveness.MethodsNinety-seven invasive-related genes obtained from the CancerSEA database were clustered to obtain the molecular subtype of pancreatic cancer based on the RNA-sequencing (RNA-seq) data of The Cancer Genome Atlas (TCGA). The differentially expressed genes (DEGs) between subtypes were obtained using the limma package in R, and the multi-gene risk model based on DEGs was constructed by Lasso regression analysis. Independent datasets GSE57495 and GSE62452 were used to validate the prognostic value of the risk model. To further explore the expression of the hub genes, immunohistochemistry was performed on PAAD tissues obtained from a large cohort.ResultsThe TCGA-PAAD samples were divided into two subtypes based on the expression of the invasion-related genes: C1 and C2. Most genes were overexpressed in the C1 subtype. The C1 subtype was mainly enriched in tumor-related signaling pathways, and the prognosis of patients with the C1 subtype was significantly worse than those with the C2 subtype. A 3-gene signature consisting of LY6D, BCAT1, and ITGB6 based on 538 DEGs between both subtypes serves as a stable prognostic marker in patients with pancreatic cancer across multiple cohorts. LY6D, BCAT1, and ITGB6 were over-expressed in 120 PAAD samples compared to normal samples.ConclusionsThe constructed 3-gene signature can be used as a molecular marker to assess the prognostic risk in patients with PAAD.

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“…Western blots were performed as described previously ( Luo et al, 2021 ). RIPA buffer (Thermo Fisher, Waltham, MA, United States) was used to extract the total protein from samples.…”

Section: Methodsmentioning

confidence: 99%

Albuca Bracteate Polysaccharides Synergistically Enhance the Anti-Tumor Efficacy of 5-Fluorouracil Against Colorectal Cancer by Modulating β-Catenin Signaling and Intestinal Flora

Xue

Tan

et al. 2021

Front. Pharmacol.

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The first-line treatment for colorectal cancer (CRC) is 5-fluorouracil (5-FU). However, the efficacy of this treatment is sometimes limited owing to chemoresistance as well as treatment-associated intestinal mucositis and other adverse events. Growing evidence suggests that certain phytochemicals have therapeutic and cancer-preventing properties. Further, the synergistic interactions between many such plant-derived products and chemotherapeutic drugs have been linked to improved therapeutic efficacy. Polysaccharides extracted from Albuca bracteata (Thunb.) J.C.Manning and Goldblatt (ABP) have been reported to exhibit anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, murine CRC cells (CT26) and a murine model of CRC were used to examine the anti-tumor properties of ABP and explore the mechanism underlying the synergistic interactions between ABP and 5-FU. Our results revealed that ABP could inhibit tumor cell proliferation, invasion, and migratory activity in vitro and inhibited tumor progression in vivo by suppressing β-catenin signaling. Additionally, treatment with a combination of ABP and 5-FU resulted in better outcomes than treatment with either agent alone. Moreover, this combination therapy resulted in the specific enrichment of Ruminococcus, Anaerostipes, and Oscillospira in the intestinal microbiota and increased fecal short-chain fatty acid (SCFA) levels (acetic acid, propionic acid, and butyric acid). The improvement in the intestinal microbiota and the increase in beneficial SCFAs contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Together, these data suggest that ABP exhibits anti-neoplastic activity and can effectively enhance the efficacy of 5-FU in CRC treatment. Therefore, further research on the application of ABP in the development of novel anti-tumor drugs and adjuvant compounds is warranted and could improve the outcomes of CRC patients.

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BCAT1 decreases the sensitivity of cancer cells to cisplatin by regulating mTOR-mediated autophagy via branched-chain amino acid metabolism

Cited by 55 publications

References 36 publications

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

HGF/c‐MET pathway contributes to cisplatin‐mediated PD‐L1 expression in hepatocellular carcinoma

Systematic Analysis of an Invasion-Related 3-Gene Signature and Its Validation as a Prognostic Model for Pancreatic Cancer

Albuca Bracteate Polysaccharides Synergistically Enhance the Anti-Tumor Efficacy of 5-Fluorouracil Against Colorectal Cancer by Modulating β-Catenin Signaling and Intestinal Flora

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