Co-targeting of EGFR and autophagy signaling is an emerging treatment strategy in metastatic colorectal cancer

Koustas, Evangelos; Karamouzis, Michalis V.; Mihailidou, Chrysovalantou; Schizas, Dimitrios; Papavassiliou, Athanasios G.

doi:10.1016/j.canlet.2017.03.023

Cited by 59 publications

(68 citation statements)

References 89 publications

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“…EGFR-TKI drugs have been used clinically for a relatively long time and are recommended by the National Comprehensive Cancer Network and European Society for Medical Oncology guidelines for the treatment of advanced NSCLC with sensitive mutations (16,17). EGFR targeting is an emerging strategy for treating other tumors, including anaplastic thyroid cancer and colorectal cancer (18,19).…”

Section: Egfr and Egfr-tkimentioning

confidence: 99%

Opportunities and challenges of co‑targeting epidermal growth factor receptor and autophagy signaling in non‑small cell lung cancer (Review)

Wang

et al. 2019

Oncol Lett

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Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are a standard therapy for patients with non-small cell lung cancer (NSCLC) with sensitive mutations. However, acquired resistance emerges following a median of 6-12 months. Several studies demonstrated that EGFR-TKI-induced tumor microenvironment stresses and autophagy are important causes of resistance. The current review summarizes the molecular mechanisms involved in EGFR-mediated regulation of autophagy. The role of autophagy in EGFR-TKI treatment, which may serve a role in protection or cell death, was discussed. Furthermore, co-inhibiting EGFR and autophagy signaling as a rational therapeutic strategy in the treatment of patients with NSCLC was explored. Contents 1. Introduction 2. EGFR and EGFR-TKI 3. Autophagy and its regulation 4. EGFR-mediated regulation of autophagy 5. Role of autophagy in EGFR-TKI treatment 6. Conclusions and perspectives

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Section: Egfr and Egfr-tkimentioning

confidence: 99%

Opportunities and challenges of co‑targeting epidermal growth factor receptor and autophagy signaling in non‑small cell lung cancer (Review)

Wang

et al. 2019

Oncol Lett

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“…However, molecular mechanisms of its pathogenesis are still not completely known. Autophagy, a process of degrading and re-using of unneeded or damaged cellular components, recently appreciated by the Nobel Prize, is important in cancer transformation and functions of a cancer cell, including metastasis [ 14 , 15 , 16 , 17 ]. Many proteins important for autophagy are regulated by lncRNAs [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

The Long Noncoding RNA HOTAIR in Breast Cancer: Does Autophagy Play a Role?

Pawłowska

Szczepańska

Błasiak

2017

IJMS

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HOTAIR (HOX transcript antisense RNA) plays a critical role in chromatin dynamics through the interaction with histone modifiers resulting in transcriptional gene silencing. The promoter of the HOTAIR gene contains multiple estrogen response elements (EREs) and is transcriptionally activated by estradiol in estrogen receptor-positive breast cancer cells. HOTAIR competes with BRCA1, a critical protein in breast cancer and is a critical regulator of genes involved in epithelial-to-mesenchymal transition. It mediates an oncogenic action of c-Myc, essential for breast carcinogenesis. The carcinogenic action of HOTAIR was confirmed in breast cancer stem-like cells, in which it was essential for self-renewal and proliferation. Several miRNAs regulate the expression of HOTAIR and HOTAIR interacts with many miRNAs to support cancer transformation. Many studies point at miR-34a as a major component of HOTAIR–miRNAs–cancer cross-talk. The most important role of HOTAIR can be attributed to cancer progression as its overexpression stimulates invasion and metastasis. HOTAIR can regulate autophagy, important for breast cancer cells survival, through the interaction with miRNAs specific for autophagy genes and directly with these genes. The role of HOTAIR-mediated autophagy in breast cancer progression can be underlined by its interaction with matrix metalloproteinases, essential for cancer invasion, and β-catenin can be important for this interaction. Therefore, there are several mechanisms of the interplay between HOTAIR and autophagy important for breast cancer, but further studies are needed to determine more details of this interplay.

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“…In lung cancer, Ras‐activated cells rely on autophagy for the generation of the tricarboxylic acid cycle to enhance cancer cell proliferation . A previous study has demonstrated that inhibition of autophagy could strongly decrease CRC metastasis . There is also a growing body of literature to suggest that the combination therapy of inhibition autophagy and chemotherapy could be a promising strategy for the treatment of CRC .…”

Section: Introductionmentioning

confidence: 99%

“…15 A previous study has demonstrated that inhibition of autophagy could strongly decrease CRC metastasis. 16 There is also a growing body of literature to suggest that the combination therapy of inhibition autophagy and chemotherapy could be a promising strategy for the treatment of CRC. 17 More importantly, in some tumors, autophagy was found to be upregulated in hypoxic regions.…”

mentioning

confidence: 99%

miR‐20a inhibits hypoxia‐induced autophagy by targeting ATG5/FIP200 in colorectal cancer

Che

Wang

Huang

et al. 2019

Molecular Carcinogenesis

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Autophagy is a highly conserved lysosome‐mediated protective cellular process in which cytosolic components, including damaged organelles and long‐lived proteins, are cleared. Many studies have shown that autophagy was upregulated in hypoxic regions. However, the precise molecular mechanism of hypoxia‐induced autophagy in colorectal cancer (CRC) is still elusive. In this study, we found that miR‐20a was significantly downregulated under hypoxia in colon cancer cells, and overexpression of miR‐20a alleviated hypoxia‐induced autophagy. Moreover, miR‐20a inhibits the hypoxia‐induced autophagic flux by targeting multiple key regulators of autophagy, including ATG5 and FIP200. Furthermore, by dual‐luciferase assay we demonstrated that miR‐20a directly targeted the 3′‐untranslated region of ATG5 and FIP200, regulating their messenger RNA and protein levels. In addition, reintroduction of exogenous ATG5 or FIP200 partially reversed miR‐20a‐mediated autophagy inhibition under hypoxia. A negative correlation between miR‐20a and its target genes is observed in the hypoxic region of colon cancer tissues. Taken together, our findings suggest that hypoxia‐mediated autophagy was regulated by miR‐20a/ATG5/FI200 signaling pathway in CRC. miR‐20a‐mediated autophagy defect that might play an important role in hypoxia‐induced autophagy during colorectal tumorigenesis.

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Co-targeting of EGFR and autophagy signaling is an emerging treatment strategy in metastatic colorectal cancer

Cited by 59 publications

References 89 publications

Opportunities and challenges of co‑targeting epidermal growth factor receptor and autophagy signaling in non‑small cell lung cancer (Review)

Opportunities and challenges of co‑targeting epidermal growth factor receptor and autophagy signaling in non‑small cell lung cancer (Review)

The Long Noncoding RNA HOTAIR in Breast Cancer: Does Autophagy Play a Role?

miR‐20a inhibits hypoxia‐induced autophagy by targeting ATG5/FIP200 in colorectal cancer

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