Autophagy Function and Dysfunction: Potential Drugs as Anti-Cancer Therapy

Cuomo, Francesca; Altucci, Lucia; Cobellis, Gilda

doi:10.3390/cancers11101465

Cited by 56 publications

(50 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results also showed that the inhibition of autophagy increased the levels of PDCD4 in HCC. Recent clinical studies for cancer treatment have attempted to therapeutically target autophagy [68,69]. The increased levels of PDCD4 by autophagy inhibition might be involved in suppressing tumor development and progression and contribute to the treatment of various cancers.…”

Section: Discussionmentioning

confidence: 99%

Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy

Manirujjaman

Ozaki

Murata

et al. 2020

Cells

View full text Add to dashboard Cite

PDCD4 (programmed cell death 4) is a tumor suppressor that plays a crucial role in multiple cellular functions, such as the control of protein synthesis and transcriptional control of some genes, the inhibition of cancer invasion and metastasis. The expression of this protein is controlled by synthesis, such as via transcription and translation, and degradation by the ubiquitin-proteasome system. The mitogens, known as tumor promotors, EGF (epidermal growth factor) and TPA (12-O-tetradecanoylphorbol-13-acetate) stimulate the degradation of PDCD4 protein. However, the whole picture of PDCD4 degradation mechanisms is still unclear, we therefore investigated the relationship between PDCD4 and autophagy. The proteasome inhibitor MG132 and the autophagy inhibitor bafilomycin A1 were found to upregulate the PDCD4 levels. PDCD4 protein levels increased synergistically in the presence of both inhibitors. Knockdown of p62/SQSTM1 (sequestosome-1), a polyubiquitin binding partner, also upregulated the PDCD4 levels. P62 and LC3 (microtubule-associated protein 1A/1B-light chain 3)-II were co-immunoprecipitated by an anti-PDCD4 antibody. Colocalization particles of PDCD4, p62 and the autophagosome marker LC3 were observed and the colocalization areas increased in the presence of autophagy and/or proteasome inhibitor(s) in Huh7 cells. In ATG (autophagy related) 5-deficient Huh7 cells in which autophagy was impaired, the PDCD4 levels were increased at the basal levels and upregulated in the presence of autophagy inhibitors. Based on the above findings, we concluded that after phosphorylation in the degron and ubiquitination, PDCD4 is degraded by both the proteasome and autophagy systems.

show abstract

Section: Discussionmentioning

confidence: 99%

Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy

Manirujjaman

Ozaki

Murata

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Research in different kinds of cancer has focused mainly on mTOR or the Akt/mTOR pathway (81)(82)(83)(84), which are signaling cascades shared between translation and autophagy. Here we review examples of molecules currently tested targeting this pathway (squematized in Figure 4).…”

Section: The Akt/mtor Pathwaymentioning

confidence: 99%

Autophagy Regulation by the Translation Machinery and Its Implications in Cancer

et al. 2020

View full text Add to dashboard Cite

Various metabolic pathways and molecular processes in the cell act intertwined, and dysregulating the interplay between some of them may lead to cancer. It is only recently that defects in the translation process, i.e., the synthesis of proteins by the ribosome using a messenger (m)RNA as a template and translation factors, have begun to gain strong attention as a cause of autophagy dysregulation with effects in different maladies, including cancer. Autophagy is an evolutionarily conserved catabolic process that degrades cytoplasmic elements in lysosomes. It maintains cellular homeostasis and preserves cell viability under various stress conditions, which is crucial for all eukaryotic cells. In this review, we discuss recent advances shedding light on the crosstalk between the translation and the autophagy machineries and its impact on tumorigenesis. We also summarize how this interaction is being the target for novel therapies to treat cancer.

show abstract

“…Autophagy, a process of phagocytosis of the cytoplasmic proteins or organelles and their inclusion into vesicles, fusion with lysosomes to form autophagy lysosomes and degradation of the contents they contain, can inhibit inflammation caused by cancer cells and stabilize cell chromosome construction [22,23]. AS-IV, an Astragalus polysaccharide with a distinct structure, is present in Astragalus in smaller amounts when compared with other polysaccharides [24].…”

Section: As-ivmentioning

confidence: 99%

Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion

Xia

Cai

2020

Cell Mol Biol Lett

View full text Add to dashboard Cite

Background: Cervical cancer remains the second leading cause of mortality in women in developing countries. While surgery, chemotherapy, radiotherapy, and vaccine therapy are being applied for its treatment, individually or in combination, the survival rate in advanced cervical cancer patients is still very low. Traditional Chinese medicine has been found to be effective in the treatment of cervical cancer. Astragaloside IV (AS-IV), a compound belonging to Astragalus polysaccharides, shows anticancer activity through several cell signaling pathways. However, the detailed molecular mechanism governing the anticancer activity of AS-IV remains unknown. Material and methods: In our study, we performed tumor xenograft analysis, transwell cell migration and invasion assay, Western blot analysis, and iTRAQ combination by parallel reaction monitoring (PRM) analysis to study the molecular mechanism of AS-IV in the suppression of cervical cancer cell invasion. Results: Our results showed that AS-IV suppressed cervical cancer cell invasion and induced autophagy in them, with the tumor growth curve increasing slowly. We also identified 32 proteins that were differentially expressed in the SiHa cells when treated with AS-IV, with 16 of them involved in the upregulation and 16 in the downregulation of these cells. These differentially expressed proteins, which were predominantly actinmyosin complexes, controlled cell proliferation and cell development by steroid binding and altering the composition of the cell cytoskeleton. DCP1A and TMSB4X, the two proteins regulating autophagy, increased in cervical cancer cells when treated with AS-IV. Conclusions: We conclude that AS-IV could inhibit cervical cancer invasion by inducing autophagy in cervical cancer cells. Since iTRAQ combination by PRM has been observed to be useful in identifying macromolecular target compounds, it may be considered as a novel strategy in the screening of anticancer compounds used in the treatment of cervical cancer.

show abstract

Autophagy Function and Dysfunction: Potential Drugs as Anti-Cancer Therapy

Cited by 56 publications

References 142 publications

Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy

Degradation of the Tumor Suppressor PDCD4 Is Impaired by the Suppression of p62/SQSTM1 and Autophagy

Autophagy Regulation by the Translation Machinery and Its Implications in Cancer

Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion

Contact Info

Product

Resources

About