NETO2 promotes esophageal cancer progression by inducing proliferation and metastasis via PI3K/AKT and ERK pathway

AbstractCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

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HNRNPH1-stabilized LINC00662 promotes ovarian cancer progression by activating the GRP78/p38 pathway

Oncogene ◽

10.1038/s41388-021-01884-5 ◽

2021 ◽

Author(s):

Yong Wu ◽

Qinhao Guo ◽

Xingzhu Ju ◽

Zhixiang Hu ◽

Lingfang Xia ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Progression ◽

Prognostic Indicator ◽

Mapk Signaling ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Proliferation And Metastasis ◽

Nuclear Ribonucleoprotein

AbstractNumerous studies suggest an important role for copy number alterations (CNAs) in cancer progression. However, CNAs of long intergenic noncoding RNAs (lincRNAs) in ovarian cancer (OC) and their potential functions have not been fully investigated. Here, based on analysis of The Cancer Genome Atlas (TCGA) database, we identified in this study an oncogenic lincRNA termed LINC00662 that exhibited a significant correlation between its CNA and its increased expression. LINC00662 overexpression is highly associated with malignant features in OC patients and is a prognostic indicator. LINC00662 significantly promotes OC cell proliferation and metastasis in vitro and in vivo. Mechanistically, LINC00662 is stabilized by heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1). Moreover, LINC00662 exerts oncogenic effects by interacting with glucose-regulated protein 78 (GRP78) and preventing its ubiquitination in OC cells, leading to activation of the oncogenic p38 MAPK signaling pathway. Taken together, our results define an oncogenic role for LINC00662 in OC progression mediated via GRP78/p38 signaling, with potential implications regarding therapeutic targets for OC.

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Tip60 Suppresses Cholangiocarcinoma Proliferation and Metastasis via PI3k-AKT

Cellular Physiology and Biochemistry ◽

10.1159/000494183 ◽

2018 ◽

Vol 50 (2) ◽

pp. 612-628 ◽

Cited By ~ 4

Author(s):

Yaodong Zhang ◽

Guwei Ji ◽

Sheng Han ◽

Zicheng Shao ◽

Zefa Lu ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Progression ◽

Venous Invasion ◽

In Vivo Studies ◽

Akt Pathway ◽

Rank Test ◽

Aberrant Expression ◽

Proliferation And Metastasis

Background/Aims: Aberrant expression of Tip60 is associated with progression in many cancers. However, the role of Tip60 in cancer progression remains contradictory. The aim of this study was to investigate the clinical significance, biological functions and underlying mechanisms of Tip60 deregulation in cholangiocarcinoma (CCA) for the first time. Methods: Quantitative real-time PCR (QRT-PCR), western blotting and immunohistochemistry staining (IHC) were carried out to measure Tip60 expression in CCA tissues and cell lines. Kaplan–Meier analysis and the log-rank test were used for survival analysis. In vitro, cell proliferation was evaluated by flow cytometry and CCK-8, colony formation, and EDU assays. Migration/ invasion was evaluated by trans-well assays. Phosphokinase array was used to confirm the dominant signal regulated by Tip60. Tumor growth and metastasis were demonstrated in vivo using a mouse model. Results: Tip60 was notably downregulated in CCA tissues, which was associated with greater tumor size, venous invasion, and TNM stage. Down-regulation of Tip60 was associated with tumor progression and poorer survival in CCA patients. In vitro and in vivo studies demonstrated that Tip60 suppressed growth and metastasis throughout the progression of CCA. We further identified the PI3K/AKT pathway as a dominant signal of Tip60 and suggested that Tip60 regulated CCA cell proliferation and metastasis via PT3K-AKT pathway. Pearson analysis revealed that PTEN was positively correlated with the Tip60 level in CCA tissues. Conclusion: Tip60, as a tumor suppressor in CCA via the PI3K/AKT pathway, might be a promising therapeutic target or prognostic marker for CCA.

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EMP3, which is regulated by miR-663a, suppresses gallbladder cancer progression via interference with the MAPK/ERK pathway

Cancer Letters ◽

10.1016/j.canlet.2018.05.022 ◽

2018 ◽

Vol 430 ◽

pp. 97-108 ◽

Cited By ~ 13

Author(s):

Qiang Ma ◽

Yijian Zhang ◽

Haibin Liang ◽

Fei Zhang ◽

Fatao Liu ◽

...

Keyword(s):

Gallbladder Cancer ◽

Cancer Progression ◽

Erk Pathway

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Epigenetically associated CCL20 upregulation correlates with esophageal cancer progression and immune disorder

Pathology - Research and Practice ◽

10.1016/j.prp.2021.153683 ◽

2021 ◽

pp. 153683

Author(s):

Hongxing Nan ◽

Lisha Zhou ◽

Weihua Liang ◽

Jin Meng ◽

Ke Lin ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Progression ◽

Immune Disorder

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Hsa_circ_0004370 promotes esophageal cancer progression through miR-1294/LASP1 pathway

Bioscience Reports ◽

10.1042/bsr20182377 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 11

Author(s):

Zhenyang Zhang ◽

Wenwei Lin ◽

Lei Gao ◽

Keqing Chen ◽

Chuangcai Yang ◽

...

Keyword(s):

Esophageal Cancer ◽

Cell Lines ◽

Cancer Progression ◽

Multiple Roles ◽

Luciferase Reporter ◽

Circular Rnas ◽

Rescue Effect ◽

Rna Immunoprecipitation ◽

Si Rna ◽

Proliferation And Invasion

AbstractCircular RNAs (circRNAs) formed by back-splicing play multiple roles in the occurrence and development of cancer. Here, we found that hsa_circ_0004370 was up-regulated in both esophageal cancer (EC) tissues and cell lines. Loss function of hsa_circ_0004370 by si-RNA significantly suppressed proliferation and invasion and promoted apoptosis in both EC cell lines. The sponging of miR-1294 by hsa_circ_0004370 was bioinformatically predicted and subsequently verified by luciferase reporter assay and RNA immunoprecipitation assay. Further, hsa_circ_0004370 involved in the up-regulation of LASP1 by sponging miR-1294. Besides, the inhibition of the down-regulated hsa_circ_0004370 on cell malignant behaviors was rescued by miR-1294 inhibitor. Finally, this rescue effect was abrogated by suppressing the expression of LASP1. The results present here suggest that hsa_circ_0004370 functions as an oncogene on cell proliferation, apoptosis, and invasion via miR-1294/LASP1 axis.

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