ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α

Wu, Fengyuan; Fang, Tian; Yu, Le-Xing; Lv, Guishuai; Lv, Hongwei; Dong, Liang; Li, Ting; Wang, Changzheng; Tan, Ye-Xiong; Ding, Jin; Chen, Yao; Tang, Liang; Guo, Linna; Tang, Shanhua; Yang, Wen; Wang, Hongyang

doi:10.1016/j.jhep.2016.04.019

Cited by 166 publications

(127 citation statements)

References 22 publications

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“…Among them, DEN-induced HCC model is the most frequently used [60, 61]. A recent study have demonstrated that autophagy inhibits HCC progression and sorafenib resistance by promoting degradation of HIF1α in the DEN-induced HCC mouse model [62]. …”

Section: Autophagy and Cancermentioning

confidence: 99%

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Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

Sun¹,

Liu²,

Ming³

2017

Cell Physiol Biochem

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Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and prognosis remains unsatisfactory since the disease is often diagnosed at the advanced stages. Currently, the multikinase inhibitor sorafenib is the only drug approved for the treatment of advanced HCC. However, primary or acquired resistance to sorafenib develops, generating a roadblock in HCC therapy. Autophagy is an intracellular lysosomal pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. Current understanding of the role of autophagy in the progression of cancer and the response to cancer therapy remains controversial. Sorafenib is able to induce autophagy in HCC, but the effect of autophagy is indistinct. Some studies established that sorafenib-induced autophagy serves as a pro-survival response. However, other studies found that sorafenib-induced autophagy improves the lethality of sorafenib against HCC cells. The mechanisms underlying autophagy and sorafenib resistance remain elusive. The purpose of this review is to summarize the progress of research focused on autophagy and sorafenib resistance and to update current knowledge of how cellular autophagy impacts sorafenib sensitivity in HCC treatment.

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Section: Autophagy and Cancermentioning

confidence: 99%

“…Conversely, inhibition of ADRB2 leads to enhanced autophagy, HIF1α destabilization, and an improved anti-tumor activity of sorafenib. These results uncover an important role of ADRB2 signaling in sorafenib resistance through inhibition of autophagy [62]. …”

Section: Autophagy and Cancermentioning

confidence: 99%

Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

Sun¹,

Liu²,

Ming³

2017

Cell Physiol Biochem

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“…Thus, autophagy-mediated alteration in metabolism contributes to reduced cellular vitality which can be a partial reason for autophagic cell death. [63] It can be hypothesized that the level of autophagy plays the dominant role in the regulation of its either pro-survival and pro-death. Autophagy regulates tumor cell survival under moderate hypoxia with no nutrient limitation while tumor cells faces autophagic cell death under severe hypoxia associated with metabolic stress.…”

Section: Autophagy As a Negative Regulator Of Hcc Survival Under Hypoxiamentioning

confidence: 99%

Hypoxia-induced autophagy in hepatocellular carcinoma and anticancer therapy

Kabir¹,

Yong²

2017

Natl J Physiol Pharm Pharmacol

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Autophagy is a genetically programmed dynamic process for the lysosomal degradation and recycling of bulk cytoplasmic contents, abnormal proteins, and damaged organelles. Along with cellular homeostasis maintenance, autophagy plays a fundamental role in cancer as tumor cells activate autophagy under stressful conditions such as hypoxia, nutrient derivation, and anticancer therapy. Increasing reports suggest the protective role of autophagy in hepatocellular carcinoma (HCC). Despite recent developments in HCC anticancer treatment, the overall patient survival remains poor. Tumor hypoxia, a common characteristic of most solid tumors like HCC is correlated with poor prognosis for patients partly because hypoxia promotes resistance to cancer therapy. Hypoxia preferentially selects apoptosis-resistant cells and activates autophagy as a survival mechanism leading to malignant and aggressive phenotype. In this review, we summarized the molecules involved in hypoxia-induced autophagy for HCC progression and anticancer therapy resistance. In addition, the molecular pathways involved in hypoxia-induced autophagy were provided. We also focused on some recent researches between hypoxia-induced autophagy and microRNAs in HCC. We believe understanding the novel function of hypoxia-regulated autophagy may coin new targets for the betterment of HCC treatment and improved clinical outcomes.

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“…Rudalska et al found elevated Mapk14-Atf2 signaling was a poor response predictor to sorafenib therapy in human HCC, and silencing Mapk14 was able to revert sorafenib resistance of p-Mapk14-expressing HCC cells (11). Wu et al demonstrated ADRB2 signaling inhibited autophagic degradation of HIF1α to promote HCC progression and sorafenib resistance (12). Zhou et al proved tumor-associated neutrophils recruit macrophages and T-regulatory cells can promote resistance to sorafenib in HCC, which illustrated immune system also played a crucial role in the response to sorafenib (13).…”

Section: Commentarymentioning

confidence: 99%

Comment on “combination treatment including targeted therapy for advanced hepatocellular carcinoma”

Zhang

2016

Hepatobiliary Surg. Nutr.

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ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α

Cited by 166 publications

References 22 publications

Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

Hypoxia-induced autophagy in hepatocellular carcinoma and anticancer therapy

Comment on “combination treatment including targeted therapy for advanced hepatocellular carcinoma”

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