LC3A, LC3B and Beclin-1 Expression in Gastric Cancer

Giatromanolaki, Alexandra; Koukourakis, Michael I.; Georgiou, Ioannis; Kouroupi, Maria; Sivridis, Efthimios

doi:10.21873/anticanres.13056

Cited by 30 publications

(32 citation statements)

References 21 publications

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“…Dysfunction of autophagy is involved in multiple human diseases (Levine and Kroemer, 2008;Liang, 2010), including cancer where autophagy plays a double role: in oncogenically challenged cells autophagy may prevent tumor progression by removing ROS and damaged mitochondria (White, 2012;Amaravadi and Debnath, 2014); on the other hand, in overt tumors, autophagy seems to contribute to tumor cell survival by promoting nutrient recycling and sustaining anti-apoptotic pathways (Levy et al, 2017;Mowers et al, 2017). Along with this line, increased autophagic flux has been reported for various types of tumors, including breast cancer (BC) (Lazova et al, 2012;Mikhaylova et al, 2012;Giatromanolaki et al, 2018).…”

Section: Introductionmentioning

confidence: 98%

The Autophagy Machinery Contributes to E-cadherin Turnover in Breast Cancer

Damiano

Spessotto

Vanin

et al. 2020

Front. Cell Dev. Biol.

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Autophagy is an intracellular catabolic process that is increasingly being recognized as a crucial factor in several human diseases including cancers. Mounting evidence suggests that autophagy allows tumor cells to overcome otherwise fatal stresses and to increase dissemination. Nevertheless, how autophagy controls these processes and in particular how it impinges on cell-cell adhesion is still poorly understood. Here, we investigate the role of autophagy in the turnover of the epithelial adhesion molecule E-cadherin in the context of breast cancer. We demonstrated in breast cancer cell lines that autophagy impinges on E-cadherin expression and in the configuration of adherens junctions. Besides, we showed that E-cadherin colocalizes with LC3B and SQSTM1/p62, two components of the autophagosome machinery. Pull down and immunoprecipitation analyses provided evidence that E-cadherin and SQSTM1/p62 physically interact. Moreover, the physical closeness of E-cadherin and SQSTM1/p62 was demonstrated by proximity ligation assays in breast cancer cell lines and primary tumors. Finally, we proved that the silencing of SQSTM1/p62 diminished the E-cadherin/LC3B colocalization, further supporting the role of SQSTM1/p62 in E-cadherin delivery to autophagosomes. These findings suggest that the activation of autophagy, reported in breast cancers with poor prognosis and in dormant breast cancer cells, may contribute to the control of tumor progression via downmodulation of E-cadherin protein levels.

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Section: Introductionmentioning

confidence: 98%

The Autophagy Machinery Contributes to E-cadherin Turnover in Breast Cancer

Damiano

Spessotto

Vanin

et al. 2020

Front. Cell Dev. Biol.

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“…Discussion. It is known that a high content of the LC3B protein of gastric tumors is one of the markers of the disease [Giatromanolaki A, 2019] and can predict the outcome of the disease . This study showed that LC3B expression is associated with tumor size and disease prevalence.…”

Section: Resultsmentioning

confidence: 99%

“…The latter is a structural protein of autophagosome membranes and is widely used as a marker of this process. High levels of LC3B are found in gastric cancer cells [Giatromanolaki A, 2019] and can predict the disease's outcome .…”

Section: Introductionmentioning

confidence: 99%

Title: Expression and content of the LC3B protein in gastric cancers, relationship to mTOR, AMPK expression, clinical and morphological parameters, and the tumor response to neoadjuvant chemotherapy

Spirina¹,

Августинович²,

Bakina³

et al. 2021

Preprint

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Background. Autophagy plays a dual role in oncogenesis processes. On the one hand, increasing the cell's resistance to oncogenic factors, and on the other hand, participating in the processes of tumor progression and the formation of resistance to antitumor treatment. It has been shown that autophagy correlates with the aggressive course of the disease and its poor prognosis. The molecular cascades that regulate autophagy are numerous and varied and play a role in tumorigenesis that has not yet been studied.The study aimed to study the expression of LC3B, mTOR, AMPK, the content of the LC3B protein in gastric cancer tissue, and its relationship with disease progression, and the response to anti-cancer therapy.Material and methods. The study included 34 patients with morphologically verified gastric cancer. All patients were hospitalized in the Department of Abdominal Oncology of the TNIMTs Research Institute of Oncology. All patients had FLOT neoadjunvant chemotherapy (NACT) (fluorouracil, leucovorin, oxaliplatin, and docetaxel) followed the gastrectomy. The response to the combined treatment of patients was evaluated according to the RECIST 1.1 criteria.The study's material was the non-transformed and tumor tissues obtained during diagnostic video gastroscopy in patients before the start of combined treatment and after surgical treatment, frozen after collection and stored at t -800C. The expression of LC3B, mTOR, AMPK was determined by real-time PCR, the LC3B protein level - using the Western Blotting method.Results and their discussion. The mRNA level and the content of the LC3B protein are associated with the size of the tumor, damage to regional lymph nodes (spread of the disease), and the presence of cricoid cells. The AMPK mRNA level increased in patients with the T4N0-2M0 stage in 37.7 and 7.33 times, respectively, compared with patients with the T2N0M0 and T3N0-1M0 stages. The opposite character in mTOR, AMPK changes in the GCs before anti-cancer therapy is noted. At the same time, the local prevalence of the tumor and the lesion of regional lymph nodes were associated with a decrease in mTOR mRNA level.A decrease in mTOR expression is accompanied by an increase in AMPK expression in a gastric tumor. It is associated, first of all, with the clinical and morphological parameters of the primary process. mTOR expression is reduced in patients with a higher local prevalence of the process; in contrast, AMPK grows with tumor size.There is an increase in the LC3B expression, which, probably, can determine the response to therapy. As a result of the study, an increase in LC3B mRNA before the start of treatment and the concentration of autophagy protein after NACT with a decrease in therapy effectiveness was recorded. An increase in the protein level in patients with partial regression and stabilization of the tumor process by 3.65 and 5.78 times compared with patients with complete tumor regression was noted. Conclusion. The development of the disease and the prediction of anticancer therapy's effectiveness is directly related to the expression level of LC3B, mTOR, and AMPK. The following relationship was revealed: a decrease in mTOR expression and an increase in the level of mRNA and protein LC3B, AMPK expression combined with the progression of the disease in the form of the development of distant metastases, as well as the predicted future low effectiveness of NACT.

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“…Inhibiting Beclin-1 has been shown with compounds such as Spautin-1, a PI3KCIII/VSP34 complex inhibitor, which targets Beclin-1-induced autophagy (Table 2) [175]. Xestosponging B can also disrupt interactions between INS Fig.…”

Section: Beclinmentioning

confidence: 99%

“…Gastric cancer has been found to have autophagy activation in all of these manners. Targeting autophagy is being investigated with both mTOR inhibition, hypoxic gene inhibition, or deacetylation inducing compounds (see Table 2) [1,4,5] P3 membrane cargo loading and Beclin-1 [175]. These compounds have been tested preclinically in gastric cancer and have shown some therapeutic benefit in gastric cancer cell lines.…”

Section: Beclinmentioning

confidence: 99%

Gastric cancer: a comprehensive review of current and future treatment strategies

Sexton

Hallak

Diab

et al. 2020

Cancer Metastasis Rev

448

251

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Gastric cancer remains a major unmet clinical problem with over 1 million new cases worldwide. It is the fourth most commonly occurring cancer in men and the seventh most commonly occurring cancer in women. A major fraction of gastric cancer has been linked to variety of pathogenic infections including but not limited to Helicobacter pylori (H. pylori) or Epstein Barr virus (EBV). Strategies are being pursued to prevent gastric cancer development such as H. pylori eradication, which has helped to prevent significant proportion of gastric cancer. Today, treatments have helped to manage this disease and the 5-year survival for stage IA and IB tumors treated with surgery are between 60 and 80%. However, patients with stage III tumors undergoing surgery have a dismal 5-year survival rate between 18 and 50% depending on the dataset. These figures indicate the need for more effective molecularly driven treatment strategies. This review discusses the molecular profile of gastric tumors, the success, and challenges with available therapeutic targets along with newer biomarkers and emerging targets.

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LC3A, LC3B and Beclin-1 Expression in Gastric Cancer

Cited by 30 publications

References 21 publications

The Autophagy Machinery Contributes to E-cadherin Turnover in Breast Cancer

The Autophagy Machinery Contributes to E-cadherin Turnover in Breast Cancer

Title: Expression and content of the LC3B protein in gastric cancers, relationship to mTOR, AMPK expression, clinical and morphological parameters, and the tumor response to neoadjuvant chemotherapy

Gastric cancer: a comprehensive review of current and future treatment strategies

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