Search

Activating molecule in Beclin-1-regulated autophagy protein 1 (Ambra1) is well known to mediate the autophagy process and promote the formation of autophagosomes. In addition, Ambra1 is involved in the execution of apoptosis. A growing number of studies have revealed that this protein modifies the sensitivity of cancer cells to anticancer drugs by controlling the balance between autophagy and apoptosis. In addition, Ambra1 is a key factor in regulating the cell cycle, proliferation, invasion and migration. Therefore, it plays a key role in tumorigenesis and progression. Moreover, Ambra1 is highly expressed in a variety of cancers and is closely related to the prognosis of patients. Thus, it appears that Ambra1 has multiple roles in tumorigenesis and progression, which may have implications for clinical oncology. The present review focuses on recent advances in the study of Ambra1, especially the role of the protein in tumorigenesis, progression and effects on anticancer drug sensitivity.

The sensitivity of cells to chemotherapeutic agents has a major effect on disease outcome in breast cancer patients. Unfortunately, there are numerous factors involved in the regulation of chemosensitivity, and the mechanisms need to be further investigated. Autophagy/Beclin 1 regulator 1 (Ambra1) is a key protein in the crosstalk between autophagy and apoptosis. It controls the switch between these two processes, which determines whether cells survive or die. Induction of apoptosis is the primary mechanism by which most chemotherapeutic drugs eliminate cancer cells. Recently, Ambra1 has been shown to modulate paclitaxel-induced apoptosis in breast cancer cells via the Bim/mitochondrial pathway, thereby modifying the sensitivity of cells to paclitaxel. However, how Ambra1 regulates Bim expression remains unclear. Here, we further confirmed that Bim plays an indispensable role in Ambra1's regulation of apoptosis and chemosensitivity in breast cancer cells. Furthermore, Ambra1 was found to regulate Bim expression at the transcriptional level through the Akt-FoxO1 pathway. Therefore, we propose a novel pathway, Ambra1-Akt-FoxO1-Bim, which regulates apoptosis and chemosensitivity in breast cancer cells. Thus, Ambra1 may represent a potential target for breast cancer treatment.

Immune checkpoint inhibitors (ICIs), especially pembrolizumab, have improved outcomes in patients with advanced or metastatic gastric cancer (GC). However, there are no reliable markers for the evaluation of its efficacy. GC samples from the UCSC Xena Browser and Gene Expression Omnibus (GEO) databases were performed by bioinformatics analysis. The single sample gene set enrichment (ssGSEA) algorithm was used to calculate the prognostic genes expression differences score (ssGSEA score) for each sample. Weighted gene co-expression network analysis (WGCNA) was applied to identify the score-related key model. The hub gene was identified based on the intersection between tumor-related transcription factors (TFs) and the key module. The predictive ability for pembrolizumab response of the hub gene was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). The correlations between the hub gene and immune infiltration in GC were investigated by the CIBERSORT algorithm. According to the ssGSEA score, patients with GC were divided into the high- and low-score group. RUNX1T1 was the hub gene of the ICIs treatment in GC. Its high expression was related to the low-score group, which indicated low sensitivity to pembrolizumab and poor prognosis. RUNX1T1 showed good predictive power for pembrolizumab response (AUC = 0.742). The CIBERSORT analysis showed that a high expression for RUNX1T1 weakened the anti-tumor immune response by affecting the immune cell infiltration.Runx1T1 may be a potential predictor of pembrolizumab efficacy in GC and be a prognostic marker for GC.

To investigate the expression of the oxidative stress proteins in human clear-cell renal cell carcinoma (CRCC) cell line (RLC-310) and normal renal proximal tubule epithelial cell line (HK-2), the CRCC and the corresponding normal renal tissues.RLC-310 and HK-2 cells were cultured in vitro. Total proteins of the two cell lines were separated by PF-2D protein fractionation system. The differentially expressed proteins of the two cell lines were analyzed using capillary LC-ESI-MS/MS and identified using the protein database. The representative differential oxidative stress proteins were verified by immunohistochemistry in the CRCC and corresponding normal renal tissues.Twelve differentially expressed oxidative stress proteins were identified, including peroxiredoxin-1, peroxiredoxin-6 (PRX-6), superoxide dismutase[Cu-Zn] SOD1, catalase, glutathione peroxidase 1, glutathione synthetase, glutathione S-transferase Pi (GSTPi), thioredoxin, heat shock protein 10 (HSP10), HSP60, HSP70 and HSP90. Three representative differential proteins PRX-6, HSP60 and GSTPi were both expressed in RLC-310 and HK-2, and the levels of these proteins were significantly higher in RLC-310 than those in HK-2 (P0.05). The levels of these proteins were significantly higher in CRCC than those in corresponding normal renal tissues (P0.05).A series of oxidative stress proteins are overexpressed in the CRCC. They play an important role in preventing oxidative damage of CRCC cells.