DCBLD2 Affects the Development of Colorectal Cancer via EMT and Angiogenesis and Modulates 5-FU Drug Resistance

Published on May 19, 2021in Frontiers in Cell and Developmental Biology5.201
· DOI :10.3389/FCELL.2021.669285
Pan Xie4
Estimated H-index: 4
(CSU: Central South University),
Fu-Qiang Yuan1
Estimated H-index: 1
(CSU: Central South University)
+ 4 AuthorsZhao-Qian Liu49
Estimated H-index: 49
(CSU: Central South University)
Sources
Abstract
Background: DCBLD2 is highly expressed in various cancers, including colorectal cancer. DCBLD2 overexpression promotes tumor occurrence, development, and metastasis. However, DCBLD2 sensitivity to chemotherapy drugs and its mechanism on tumor development are unknown. Methods: DCBLD2 expression differences in cancer and normal tissues were obtained from GEO and TCGA databases. DCBLD2 influence on prognosis was also compared, and the database analysis results were verified via the analysis of clinical samples. GDSC database was used to analyze the effect of DCBLD2 expression difference on 5-FU drug sensitivity on tumor cells. CCK-8, clone formation, scratch, Transwell invasion and migration assays were used to assess DCBLD2 effects on the proliferation, metastasis, and 5-FU drug sensitivity on HCT116 and Caco-2 colorectal cancer cells. Angiogenesis and Matrigel plug assays were used to study the effect of DCBLD2 on angiogenesis. Q-RCR and Western Blot were used to analyze DCBLD2 impact on the EMT signaling pathway, and TAP-MS assay with Co-IP verification was used to identify the downstream target proteins binding to DCBLD2. Results: Both database and clinical sample validation results showed that the expression of DCBLD2 in colorectal cancer tissues was significantly higher than that in normal tissues, leading to poor prognosis of patients. GDSC database analysis showed that DCBLD2 overexpression caused tumor cell resistance to 5-FU. The results of in vitro and in vivo experiments showed that the inhibition of DCBLD2 reduced the proliferation, migration and invasion of colorectal cancer cells, and inhibited the angiogenesis of endothelial cells, thus enhanced the drug sensitivity to 5-FU. The results of q-RCR and Western Blot experiments showed that the inhibition of DCBLD2 could enhanced the drug sensitivity to 5-FU via inhibiting the EMT. The results of TAP-MS assay showed that the proteins bound to DCBLD2 were enriched to the Focal adhesion pathway. The results of Co-IP assay show that DCBLD2 can combine with ITGB1, the key factor of Focal adhesion pathway. Conclusion: DCBLD2 may affect the development of colorectal cancer by regulating cell proliferation and motility, and modulate 5-FU resistance. DCBLD2 regulates the sensitivity of 5-FU by affecting EMT and angiogenesis. DCBLD2 and ITGB1 can interact with each other.
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#1Yuexian LiH-Index: 2
#2Cheng SunH-Index: 4
Last. Huawei ZouH-Index: 6
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Objectives: Radiotherapy has played a limited role in the treatment of non-small cell lung cancer (NSCLC) due to the risk of tumour radioresistance. We previously established the radioresistant non-small cell lung cancer (NSCLC) cell line H460R. In this study, we identified differentially expressed genes between these radioresistant H460R cells and their radiosensitive parent line. We further evaluated the role of a differentially expressed gene, ITGB1, in NSCLC cell radioresistance and as a pot...
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#1Dan Guo (Xi'an Jiaotong University)H-Index: 6
#2Dan Zhang (Xi'an Jiaotong University)H-Index: 6
Last. Yarui Li (Xi'an Jiaotong University)H-Index: 8
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Our research aims to identify the role of thrombospondin 4 (THBS4) in hepatocellular carcinoma (HCC). First, bioinformatic analysis was applied for detection the expression of THBS4 in HCC samples, and qRT-PCR and western blot were performed to explore the expression of THBS4 in HCC tissues and adjacent samples. Next, colony formation assay and cell viability assay were used to assess the function of THBS4 on HCC cells growth while transwell assay and scratch test were for metastasis. Meanwhile ...
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#1Edward Chu (University of Pittsburgh)H-Index: 47
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#1Pan Xie (CSU: Central South University)H-Index: 4
#2Jun-Luan MoH-Index: 2
Last. Zhao-Qian Liu (CSU: Central South University)H-Index: 49
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BACKGROUND Colorectal cancer (CRC) is a disease with high morbidity and mortality rates. 5-fluorouracil (5-FU) is the first-line recommended drug for chemotherapy in patients with CRC, and it has a good effect on a variety of other solid tumors as well. Unfortunately, however, due to the emergence of drug resistance the effectiveness of treatment may be greatly reduced. In the past decade, major progress has been made in the field of 5-FU drug resistance in terms of molecular mechanisms, pre-cli...
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: This study aims to investigate how Maspin affects the EMT and angiogenesis of gastric cancer (GC) cells via ITGB1/FAK pathway. Immunohistochemistry was used to evaluate the expressions of Maspin, ITGB1, FAK, E-cadherin, Vimentin, D2-40, and CD34 in GC and adjacent normal tissues from 160 patients. Then, the human GC cells with different degree of differentiation were transfected with Maspin CRISPR activation plasmid, ITGB1 siRNA and/or Maspin siRNA, followed by the following experiments, inclu...
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#1Rebecca L. Siegel (ACS: American Cancer Society)H-Index: 67
#2Kimberly D. Miller (ACS: American Cancer Society)H-Index: 28
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Colorectal cancer (CRC) is the second most common cause of cancer death in the United States. Every 3 years, the American Cancer Society provides an update of CRC occurrence based on incidence data (available through 2016) from population-based cancer registries and mortality data (through 2017) from the National Center for Health Statistics. In 2020, approximately 147,950 individuals will be diagnosed with CRC and 53,200 will die from the disease, including 17,930 cases and 3,640 deaths in indi...
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#1Jie He (Guangzhou Medical University)H-Index: 7
#2Hongli Huang (Guangzhou Medical University)H-Index: 3
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PURPOSE: DCBLD2 expression dysregulation has been reported in several types of human cancer. As yet, however, the role of DCBLD2 in colorectal cancer (CRC) is not known. METHODS: CRC tissues were obtained from patients undergoing surgery from February 2009 to May 2014 (n = 90). Tissue microarray construction and immunohistochemistry were carried out to determine DCBLD2 expression. In vivo studies were performed in 4-week-old BALB/c nude mice. In vitro studies were conducted using CRC-derived HT2...
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#1Mengmeng Cheng (HUST: Huazhong University of Science and Technology)H-Index: 1
#2Yannan Jiang (Nanjing Medical University)H-Index: 1
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Chemoresistance is a leading cause of tumor relapse and treatment failure in colorectal cancer (CRC) patients and is correlated with epithelial-mesenchymal transition (EMT). This study was aimed to explore the mechanism of EMT in chemoresistant CRC. Bioinformatic method was used to screen differentially expressed genes between 5-FU sensitive and resistant CRC cells. Immunohistochemistry staining was utilized to analyze the expression of FLNA in CRC tissues. The roles of FLNA in chemoresistance w...
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#1Rebecca L. Siegel (ACS: American Cancer Society)H-Index: 67
#2Kimberly D. Miller (ACS: American Cancer Society)H-Index: 28
Last. Ahmedin Jemal (ACS: American Cancer Society)H-Index: 140
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Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2016) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2017) were collected by the National Center for Health Statis...
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#1Ling Wei (Academy of Medical Sciences, United Kingdom)H-Index: 4
#1Ling Wei (Peking Union Medical College)H-Index: 61
Last. Ming Yang (Peking Union Medical College)H-Index: 7
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Background Colorectal cancer (CRC) is the third most prevalent cancer in the world and one of the most lethal human malignancies. Chemotherapy with 5-fluorouracil, platinum, hydroxycamptothecin, vincristine, methotrexate, irinotecan, paclitaxel and/or cetuximab has significantly improved the survival of CRC patients. However, most CRC patients eventually develop chemoresistance, resulting in a poor prognosis. The mechanisms involved in CRC chemoresistance are complex and, as yet, inconclusive. N...
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