ALC1 knockdown enhances cisplatin cytotoxicity of esophageal squamous cell carcinoma cells by inhibition of glycolysis through PI3K/Akt pathway

Publication date: 1 September 2019Source: Life Sciences, Volume 232Author(s): Fangfang Li, Zhen Zhang, Peng Wang, Penghao Wen, Quanxiao Xu, Yunlong Wang, Ping Pan, Lei MaAbstractAimsAmplified in liver cancer 1 gene (ALC1), a recently identified oncogene, was reported to be overexpressed in esophageal cancer cell lines and identified as a target oncogene in esophageal cancer pathogenesis. However, little literature is available to illustrate its significance in cisplatin resistance of esophageal squamous cell carcinoma (ESCC) cells. The aim of the current study was to investigate the effect of ALC1 on cisplatin cytotoxicity of ESCC cells and to study the potential mechanisms.Main methodsALC1 at mRNA and protein levels were detected by qRT-PCR and western blot, respectively. Cell viability was evaluated using CCK-8 assay. Apoptosis was assessed using caspase-3/7 activity assay and flow cytometry analysis. Glycolysis level was evaluated by measuring glucose consumption and lactate production. The protein levels of p-protein kinase B (Akt) and Akt were determined by western blot.Key findingsALC1 was highly expressed in ESCC cells compared with human normal esophageal epithelial Het-1A cells. ALC1 knockdown suppressed the viability, induced apoptosis and enhanced cisplatin cytotoxicity in ESCC cells. In addition, ALC1 knockdown inhibited glycolysis and inactivated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in ESCC cells. Mechanistically, activation of the PI3K/Akt pathwa...
Source: Life Sciences - Category: Biology Source Type: research

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In conclusion, these findings indicated that HCRP1 suppressed ESCC cell proliferation and invasion through regulation of the Wnt/β-catenin pathway. Therefore, HCRP1 may function as a tumor suppressor in ESCC progression. PMID: 31152734 [PubMed - as supplied by publisher]
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
This study is an important step forward in highlighting C1q as a new prognostic candidate biomarker for a range of carcinomas. Methods Oncomine Database Analysis The expression levels of C1QA, C1QB, and C1QC genes in various carcinomas were analyzed using Oncomine (www.oncomine.org), a cancer microarray database and web-based data mining platform from genome-wide expression analyses (22, 23). We compared the differences in mRNA level between normal tissue and carcinoma. The mRNA expression levels in neoplastic tissues compared to the healthy tissues were obtained as the parameters of p-value 2, and gene ranking in the t...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Santosh K. Ghosh1*, Thomas S. McCormick1,2 and Aaron Weinberg1* 1Biological Sciences, School of Dental Medicine, Case Western Reserve University, Cleveland, OH, United States 2Dermatology, School of Medicine, Case Western Reserve University, Cleveland, OH, United States Human beta-defensins (hBDs, −1, 2, 3) are a family of epithelial cell derived antimicrobial peptides (AMPs) that protect mucosal membranes from microbial challenges. In addition to their antimicrobial activities, they possess other functions; e.g., cell activation, proliferation, regulation of cytokine/chemokine production, migration, diffe...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Eleonora A. Braga1*†, Marina V. Fridman2†, Vitaly I. Loginov1,3, Alexey A. Dmitriev4 and Sergey G. Morozov1 1Institute of General Pathology and Pathophysiology, Moscow, Russia 2Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia 3Research Center of Medical Genetics, Moscow, Russia 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer, and it has the highest mortality rate. The increasing drug resistance of metastatic ccRCC has resulted in the search f...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Junhui Zhang1,2†, Lingfei Li1,2†, Qiong Zhang1,2, Xu Yang3, Can Zhang4, Xingyue Zhang1,2, Dongxia Zhang1,2, Yanling Lv1,2, Huapei Song1,2, Bing Chen5, Yao Liu6, Jiongyu Hu2,5*† and Yuesheng Huang1,2*† 1Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China 2State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China 3Department of Respiratory Medicine, The 983 Hospital of Joint Logistics Support Force of the Chinese Peopl...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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