Annexin A3 depletion overcomes resistance to oxaliplatin in colorectal cancer via the MAPK signaling pathway

2019 ◽  
Vol 120 (9) ◽  
pp. 14585-14593 ◽  
Author(s):  
Ruisi Xu ◽  
Jian Yin ◽  
Ying Zhang ◽  
Siqi Zhang
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Annexin A3

The potential role of regulatory microRNAs of RAS/MAPK signaling pathway in the pathogenesis of colorectal cancer

2019 ◽  
Vol 120 (12) ◽  
pp. 19245-19253 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Nikoo Saeedi ◽  
Rana Ghaffarian ◽  
Majid Khazaei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Potential Role ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals TIMP-2 Regulates 5-Fu Resistance via the ERK/MAPK Signaling Pathway in Colorectal Cancer

2020 ◽  
Author(s):  
Guolin Zhang ◽  
Xin Luo ◽  
Jianbin Xu ◽  
Wei Zhang ◽  
Engeng Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Resistance Mechanism ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Erk Mapk ◽  
Colorectal Cancer Patients ◽  
Autocrine Mechanism

Abstract Background: 5-Fluorouracil (5-Fu) is the first-line chemotherapeutic drug in the treatment of colorectal cancer. The efficiency of 5-Fu is limited by drug resistance in colorectal cancer patients. This study was aimed to define the functions of tissue inhibitor metalloproteinases 2 (TIMP-2) in the 5-Fu resistance to colorectal cancer and investigate its potential mechanism.Methods: Cytokine array, ELISA and RT-qPCR were performed to detect cytokine expression levels. Western blot and immunohistochemistry were used to show the differential expression of proteins. In addition, cell viability was detected by CCK-8.Results: We established that there is an up-regulation in the expression of the TIMP-2 in colorectal cancer patients. This up-regulation in TIMP-2 expression was evident in 5-Fu resistant colorectal cancer patients and resulted in a poor prognosis. Besides, in vivo, clinical studies and patient-derived xenograft (PDX) models confirmed that TIMP-2 was highly expressed in the 5-Fu-resistant colorectal cancer. We deduced an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway via an autocrine mechanism. The 5-Fu resistance could overcome by the inhibition of TIMP-2 by anti-TIMP-2 antibody or ERK/MAPK by U0126.Conclusion: Our findings identify a TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism in colorectal cancer. Moreover, we recommend the use of an ERK/MAPK signal pathway inhibitor or TIMP-2-mediated immunotherapy for 5-Fu resistant colorectal cancer.

scholarly journals STOML2 Interacts with PHB through Activating MAPK Signaling Pathway to Promote Colorectal Cancer Proliferation.

2020 ◽  
Author(s):  
Wenhui Ma ◽  
Yuehong Chen ◽  
Wenyi Li ◽  
Zhuoluo Xu ◽  
Zhigang Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Regulatory Mechanism ◽  
Biological Process ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Interacting Proteins ◽  
Yeast Two Hybrid ◽  
Cancer Proliferation ◽  
Two Hybrid

Abstract BackgroundOverexpression of STOML2 has been widely reported in a variety of cancer, yet few has detailed its function and regulatory mechanism. This study aims to reveal the clinicopathologic significance and oncologic function of STOML2 in colorectal cancer, explore its specific mechanism by means of yeast two-hybrid assay and bioinformatics.MethodsExpression level of STOML2 in normal colon and CRC tissue from biobank in Nanfang Hospital was detected by pathologic methods. The malignant proliferation of CRC induced by STOML2 was validated via gain-of-function and loss-of-function experiments, with novel techniques applied, such as organoid culture, orthotopic model and endoscopy monitoring. Yeast two-hybrid assay was conducted to screen interacting proteins of STOML2, followed by bioinformatics to predict biological process and signaling pathway of candidate proteins. Target protein with most functional similarity to STOML2 was validated with co-immunoprecipitation, and immunofluorescence were conducted to co-localize STOML2 and PHB. Pathway regulated by STOML2 was detected with immunoblotting, and subsequent experimental therapy was conducted with RAF inhibitor Sorafenib.ResultsSTOML2 was significantly overexpressed in colorectal cancer and its elevation was associated with unfavorable prognosis. Knockdown of STOML2 suppressed proliferation of colorectal cancer, thus attenuated subcutaneous and orthotopic tumor growth, while overexpressed STOML2 promoted proliferation in cell lines and organoids. A list of 13 interacting proteins was screened out by yeast two-hybrid assay. DTYMK and PHB were identified to be most similar to STOML2 according to bioinformatics in terms of biological process and signaling pathways; however, co-immunoprecipitation confirmed interaction between STOML2 and PHB, rather than DTYMK, despite its highest rank in previous analysis. Co-localization between STOML2 and PHB was confirmed in cell lines and tissue level. Furthermore, knockdown of STOML2 downregulated phosphorylation of RAF1, MEK1/2, ERK1/2 and ELK1 on the MAPK signaling pathway, indicating common pathway activated by STOML2 and PHB in colorectal cancer proliferation.ConclusionsThis study demonstrated that in colorectal cancer, STOML2 expression is elevated and interacts with PHB through activating MAPK signaling pathway, to promote proliferation both in vitro and in vivo. In addition, combination of screening assay and bioinformatics marks great significance in methodology to explore regulatory mechanism of protein of interest.

C8orf48 inhibits the tumorigenesis of colorectal cancer by regulating the MAPK signaling pathway

Life Sciences ◽  
2021 ◽  
Vol 266 ◽  
pp. 118872
Author(s):  
Lei Lei ◽  
Guoyan An ◽  
Ziqing Zhu ◽  
Shuzhen Liu ◽  
Yutong Fu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer

Aging ◽  
2022 ◽  
Author(s):  
Guolin Zhang ◽  
Xin Luo ◽  
Zian Wang ◽  
Jianbin Xu ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Erk Mapk

scholarly journals Aldolase A Promotes Proliferation and Metastasis of Colorectal Cancer through Targeting COPS6 and Regulating MAPK Signaling Pathway

2021 ◽  
Author(s):  
Ya Lu ◽  
Yuan Zhang ◽  
Hui Zhang ◽  
Yue Zhu ◽  
Junying Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Invasion And Migration ◽  
Proliferation And Metastasis ◽  
And Migration ◽  
Aldolase A

Abstract Background: Colorectal cancer (CRC) is a serious threat to human health, and its underlying mechanisms needs further explored. Aldolase A (ALDOA) has received increasing attention for its reported association with multiple cancers, but the function and mechanism of ALDOA in CRC remain unclear. We aimed to evaluate the biological role of ALDOA in CRC.Methods: The stable ALDOA knockdown or overexpression cell lines were established for subsequent experiments. The qRT-PCR and western blotting were used to detect the expression of ALDOA and COPS6 and the relative protein levels of epithelial-mesenchymal transition (EMT) and MAPK signaling pathway. Immunofluorescence (IF) assay was applied to determine ALDOA localization. CCK-8, transwell, and wound healing assays were performed to evaluate CRC cell proliferation, invasion, and migration. Mouse xenograft models were established to verify the effect of ALDOA on CRC cell growth in vivo. Immunoprecipitation (IP) assay and mass spectrometry (MS) analysis were conducted to identify the interactions between ALDOA and COPS6.Results: ALDOA was overexpressed in CRC tissues and cell lines. Silencing ALDOA significantly impaired the proliferation, invasion and migration of CRC cells in vitro, and obviously decreased the growth of CRC cells in vivo. Mechanically, ALDOA bound to and regulated COPS6, and the promoting effects of upregulated ALDOA on CRC cell proliferation and metastasis were inhibited by the depletion of COPS6. Besides, EMT program and MAPK signaling pathway were activated by ALDOA overexpression.Conclusion: ALDOA facilitated the proliferation, invasion and migration of CRC through binding and regulating COPS6, inducing EMT and activating MAPK signaling pathway.

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