ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition

Li, Yuexian; Sun, Chengyi; Tan, Yulong; Zhang, Heying; Li, Yuchao; Zou, Huawei

doi:10.7150/ijbs.52319

Cited by 58 publications

(44 citation statements)

References 68 publications

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“…[28] During EMT, not only the interactions of cell-cell and cell-extracellular matrix are remodeled, but also the cancer stem cell properties, enhanced DNA damage response and antioxidant activity abilities are obtained. [29,30] In this study, we found that irradiation induction promoted ZIP7 and ZEB1 expression, and the occurrence of EMT. Knockdown of ZIP7 could downregulate ZEB1 expression, but upregulate Ecadherin expression, and both of which could be partially reversed by Py treatment.…”

Section: Discussionsupporting

confidence: 52%

ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition

Nie

Sun

Pan

et al. 2021

Preprint

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Background: Irradiation-induced radioresistance often leads to the therapeutic failure of colon cancer. By regulating the redistribution of intracellular zinc, ZIP7 plays a dominating role in the activation of many critical signaling pathways in the progression of tumors. However, the relationship between ZIP7 and radioresistance is still unclear. Methods: ZIP7 expression of colon cancer was evaluated by analyzing public data from the GEPIA and CPTAC databases and validated based on immunohistochemistry (IHC) staining. Clonogenic survival assay was employed to examine the influence of intracellular zinc interference and ZIP7 knockdown on radioresistance of colon cancer, based on radioresistant colon cancer cells. At last, Western blot was performed to preliminarily explore the potential mechanisms. Results: ZIP7 was significantly upregulated in human colon cancers compared with adjacent normal tissues. ZIP7 knockdown could significantly reduce the radioresistance of colon cancer cells, while transmembrane ionophore of zinc could partially reverse this effect. In terms of mechanisms, ZIP7 knockdown significantly reversed the radiation-induced expression of elevated ZEB1 and down-regulated E-cadherin through regulating zinc. Conclusion: ZIP7 is crucial to maintain radioresistance of colon cancer cells through regulation of zinc distribution, and at least partially by maintenance of epithelial-mesenchymal transition (EMT).

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Section: Discussionsupporting

confidence: 52%

ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition

Nie

Sun

Pan

et al. 2021

Preprint

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“…Integrins provide yet another link between ECM structure and DNA damage-induced apoptosis ( Hoyt et al, 1996 ; Sethi et al, 1999 ; Hodkinson et al, 2006 ; Jinushi et al, 2012 ; Ahmed et al, 2018 ; Kowalski-Chauvel et al, 2018 ; Hou et al, 2019 ; Jung et al, 2019 ; Naci et al, 2019 ; Li et al, 2021 ). Nevertheless, the connection between adhesion and apoptosis is not linear and integrin binding to the ECM can either promote or prevent cells, in particular cancer cells, from undergoing apoptosis.…”

Section: The Impact Of Dna Damage On Ecm Remodelingmentioning

confidence: 99%

Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components

et al. 2021

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Cells are subjected to endogenous [e.g., reactive oxygen species (ROS), replication stress] and exogenous insults (e.g., UV light, ionizing radiation, and certain chemicals), which can affect the synthesis and/or stability of different macromolecules required for cell and tissue function. Oxidative stress, caused by excess ROS, and DNA damage, triggered in response to different sources, are countered and resolved by specific mechanisms, allowing the normal physiological equilibrium of cells and tissues to be restored. One process that is affected by oxidative stress and DNA damage is extracellular matrix (ECM) remodeling, which is a continuous and highly controlled mechanism that allows tissues to readjust in reaction to different challenges. The crosstalk between oxidative stress/DNA damage and ECM remodeling is not unidirectional. Quite on the contrary, mutations in ECM genes have a strong impact on tissue homeostasis and are characterized by increased oxidative stress and potentially also accumulation of DNA damage. In this review, we will discuss how oxidative stress and DNA damage affect the expression and deposition of ECM molecules and conversely how mutations in genes encoding ECM components trigger accumulation of oxidative stress and DNA damage. Both situations hamper the reestablishment of cell and tissue homeostasis, with negative impacts on tissue and organ function, which can be a driver for severe pathological conditions.

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“…We found six key proteins of focal adhesion pathway, SHC1, ACTB, ACTN1, COL1A1, FLNA, ITGB1, and MYL12B, in the results of mass spectrometry. Previous studies have shown that the activation of ITGB1/FAK pathway signal can promote EMT and angiogenesis in lung cancer, liver cancer and non-small cell lung cancer ( Guo et al, 2020 ; Wang and Chang, 2020 ; Li et al, 2021 ). The expression and localization of DCBLD2 on the cell membrane showed obvious polarity like ITGB1 when HCT116 cells were cultured in 3D condition, which was consistent with the phenotype of focal adhesion.…”

Section: Discussionmentioning

confidence: 99%

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

Xie

Yuan

Huang

et al. 2021

Front. Cell Dev. Biol.

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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, inhibited the angiogenesis of endothelial cells, and enhanced the drug sensitivity to 5-FU. The results of q-RCR and Western Blot experiments showed that the inhibition of DCBLD2 can suppress the EMT signal. 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. Down-regulation of DCBLD2 can inhibit EMT signal and angiogenesis. DCBLD2 can combine with ITGB1, the key signal factor of the Focal adhesion pathway.

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ITGB1 enhances the Radioresistance of human Non-small Cell Lung Cancer Cells by modulating the DNA damage response and YAP1-induced Epithelial-mesenchymal Transition

Cited by 58 publications

References 68 publications

ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition

ZIP7 Maintains Colon Cancer Radioresistance by Regulating Zinc-dependent Epithelial-mesenchymal Transition

Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components

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

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