TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway

Song, Guohe; Xu, Shifeng; Zhang, Hong; Wang, Yupeng; Xiao, Chao; Jiang, Tao; Wu, Leilei; Zhang, Tao; Sun, Xiaojiang; Zhong, Lin; Zhou, Chongzhi; Wang, Zhaowen; Peng, Zhihai; Chen, Jian; Wang, Xiaoliang

doi:10.1186/s13046-016-0427-7

Cited by 209 publications

(193 citation statements)

References 30 publications

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“…To further investigate the cause, focus was placed on the apoptosis signaling pathway. It has been reported that apoptosis is related to Akt activation in many cancers and targeting the PI3K/Akt pathway may suppress tumorigenesis and induce cell death . As shown, treatment combining hyperthermia and RTX significantly reduced Akt phosphorylation (p‐Akt), compared with RTX treatment alone (Figure F).…”

Section: Resultsmentioning

confidence: 70%

17‐allylamino‐17‐demethoxygeldanamycin impeded chemotherapy through antioxidant activation via reducing reactive oxygen species‐induced cell death

Chen

Qiu

et al. 2018

J of Cellular Biochemistry

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Hyperthermia enhances the anticancer effects of thymidylate synthase (TYMS) inhibitors (raltitrexed, RTX) and improves the precise biochemical mechanisms partially through enhancement of intracellular drug absorption. Recent research focuses on the potential anticancer drug target Heat Shock Protein 90 (HSP90), which could increase the sensitivity of cancer cells to TYMS inhibitors; however, with different HSP90 inhibitors, several research studies finally showed a poor efficacy in preclinical or clinical research. Here, we showed that 17‐allylamino‐17‐demethoxygeldanamycin (17‐AAG, HSP90 inhibitor) affects the efficacy of chemotherapy through antioxidant activation–induced resistance. In this study, we found that RTX, alone or in combination with hyperthermia, triggers reactive oxygen species (ROS) exposure and thus induces cell death. Also, the addition of hyperthermia showed more ROS exposure and function. The pharmacologic inhibition of HSP90 reversed the effects of chemotherapeutical treatments, while the overexpression of HSP90 showed no relation with these effects, which demonstrated that dysregulation of HSP90 might have a significant impact on chemotherapeutic treatments. The addition of 17‐AAG increased the activation of antioxidant with increased antioxidant enzymes, thus affecting the RTX efficacy.

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Section: Resultsmentioning

confidence: 70%

17‐allylamino‐17‐demethoxygeldanamycin impeded chemotherapy through antioxidant activation via reducing reactive oxygen species‐induced cell death

Chen

Qiu

et al. 2018

J of Cellular Biochemistry

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“…Huang [40], Zeng [41], and Zuo [42] et al demonstrated that the expression levels of TIMP1 may be negatively correlated with the prognosis of COAD patients. Song et al [43] found that TIMP1 knockdown could result in decreased proliferation, migration, and invasion as well as increased apoptosis in vitro, whereas there is weakened tumorigenesis and metastasis in vivo via the FAK-PI3K/Akt and MAPK pathways. The elevated TIMP1 levels in serum were related to lower tumor grade and shorter overall survival times of CRC patients [44].…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of 3 key genes associated with survival and prognosis of patients with colon adenocarcinoma via integrated bioinformatics analysis

Liu¹,

Li²,

Dong

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most lethal malignancy in the world, wherein colon adenocarcinoma (COAD) is the most prevalent type of CRC.Exploring biomarkers is important for the diagnosis, treatment, and prevention of COAD. Methods: We used GEO2R and Venn online software for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software, real-time PCR and immunohistochemistry. Results: In this study, we screened 323 common differentially expressed genes from four GSE datasets. Furthermore, four hub genes were selected for survival correlation analysis and expression level verification, three of which were shown to be statistically significant. Conclusion: Our study suggests that SERPINE1, SPP1 and TIMP1 may be biomarkers closely related to the prognosis of CRC patients.

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“…Tissue inhibitors of metalloproteases (TIMPs) have been implicated in tumourigenesis. TIMP1 overexpression is associated with advanced stages of CRC [109]. IHC studies have demonstrated a significant correlation between TIMP2 expression in inflammatory cells, increasing tumor size, lymph node involvement and presence of metastasis [110].…”

Section: Tissue Inhibitors Of Metalloproteasesmentioning

confidence: 99%

Finding Needles in Haystacks: The Use of Quantitative Proteomics for the Early Detection of Colorectal Cancer

Gould¹,

Jamaluddin²,

Petit³

et al. 2019

Advances in the Molecular Understanding of Colorectal Cancer

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Colorectal cancer (CRC) is a common and treatable disease if diagnosed early. Current population screening programs are suboptimal, and consequently, there is a need for the development of new methodologies for early diagnosis of CRC. In the past 10 years, unprecedented technological advancements in the field of mass spectrometry (MS)-based proteomics have progressively increased the sophistication and utility of these investigations, leading to the draft mapping of the human proteome. These exciting studies have shaped our mechanistic understanding of the human genome and begun to provide us with a suite of novel biomarkers to predict the onset, progression and severity of many debilitating diseases. Thus, sophisticated MS workflows coupled with revolutionary protein quantification techniques hold promise for the field of MS-based plasma proteomics, particularly valuable in the context of early stage identification of curable CRC. However, within the last 40 years, no new plasma protein biomarkers of CRC have been translated into clinical practice. Here. we discuss the application of proteomic technologies within the field of CRC, highlighting contemporary MS-based plasma proteomic strategies that could be exploited to deliver on the promise of a panel of sensitive and specific plasma-based biomarkers with which to non-invasively detect early stage CRC.

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TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway

Cited by 209 publications

References 30 publications

17‐allylamino‐17‐demethoxygeldanamycin impeded chemotherapy through antioxidant activation via reducing reactive oxygen species‐induced cell death

17‐allylamino‐17‐demethoxygeldanamycin impeded chemotherapy through antioxidant activation via reducing reactive oxygen species‐induced cell death

Identification and verification of 3 key genes associated with survival and prognosis of patients with colon adenocarcinoma via integrated bioinformatics analysis

Finding Needles in Haystacks: The Use of Quantitative Proteomics for the Early Detection of Colorectal Cancer

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