P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice by increasing tissue stiffness

Chen, Qi; Li, Jian; Guo, Sen; M, Li; Y, Li; Q, Zhang; Zheng, Lianfang; He, Xiaozhou; Zheng, Xiaofang; He, Yu; Wang, L; Bian, Wei

doi:10.7150/ijbs.16405

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…[ 58 , 59 ], ECM-transforming enzymes e.g. matrix metalloproteinases (MMPs) [ 60 , 61 ], lysyl oxidase (LOX) [ [62] , [63] , [64] ], transglutaminase [ 51 , 65 ] and. orchestrating topographic reconfiguration of the stroma, such as alignment of ECM fibers, amid the plethora of aforementioned activities.…”

Section: Evolution Of Differential Stiffness and Pro-metastatic Archimentioning

confidence: 99%

Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review

Emon

Bauer

Jain

et al. 2018

Computational and Structural Biotechnology Journal

206

178

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The role of tumor microenvironment in cancer progression is gaining significant attention. It is realized that cancer cells and the corresponding stroma co-evolve with time. Cancer cells recruit and transform the stromal cells, which in turn remodel the extra cellular matrix of the stroma. This complex interaction between the stroma and the cancer cells results in a dynamic feed-forward/feed-back loop with biochemical and biophysical cues that assist metastatic transition of the cancer cells. Although biochemistry has long been studied for the understanding of cancer progression, biophysical signaling is emerging as a critical paradigm determining cancer metastasis. In this mini review, we discuss the role of one of the biophysical cues, mostly the mechanical stiffness of tumor microenvironment, in cancer progression and its clinical implications.

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Section: Evolution Of Differential Stiffness and Pro-metastatic Archimentioning

confidence: 99%

Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review

Emon

Bauer

Jain

et al. 2018

Computational and Structural Biotechnology Journal

206

178

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show abstract

“…LOX is a secreted, copper-dependent amine oxidase and collagen cross-linker 13 . Our preliminary study showed that up-regulation of LOX expression can increase tumor stiffness, thereby promoting insulinoma growth in Rip1-Tag2 mice and that the LOX inhibitor, β-aminopropionitrile (BAPN), could inhibit tumor progression through decreasing the amount of collagen cross-links in tumors 14 .…”

Section: Introductionmentioning

confidence: 96%

Human colorectal cancer progression correlates with LOX-induced ECM stiffening

et al. 2017

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Some solid tumors are characterized by extracellular matrix (ECM) remodeling and stiffening, which is related to solid tumor progression and aggression. However, the relationship between ECM stiffness and colorectal cancer (CRC) remains unclear. In this study, we investigated the relevance of ECM stiffness to clinicopathologic features using human CRC tissue microarrays. The results demonstrate that the expression of ECM components in CRC tissues is closely correlated with CRC progression and poor prognosis, which indicates that ECM stiffness may be associated with CRC development. We further studied lysyl oxidase (LOX) expression in CRC tissue and demonstrated that LOX expression is closely correlated with CRC progression. Previous studies showed that P-selectin-mediated platelet accumulation in CRC tissue may up-regulate LOX expression. Our findings indicate that P-selectin-mediated platelet aggregation may up-regulate LOX expression and enhance the remodeling and stiffening of the tumor ECM, which may promote the progression of colorectal cancer. Therefore, LOX may be a potential effective therapeutic target to treat colorectal cancer.

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“…β-aminopropionitrile (BAPN), a well-recognized inhibitor of LOX activity. Previous researches had proved that BAPN decreases tissue stiffness in mice with insulinomas 20 . The results indicated that the tumor volumes in BAPN group were significantly smaller than those in the control group (Figure 7 B, C, p < 0.05).…”

Section: Resultsmentioning

confidence: 99%

Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma

Cai¹,

Chen²,

Jiang³

et al. 2023

Int. J. Biol. Sci.

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Emerging studies have revealed matrix stiffness promotes hepatocellular carcinoma (HCC) development. We studied metabolic dysregulation in HCC using the TCGA-LIHC database (n=374) and GEO datasets (GSE14520). HCC samples were classified into three heterogeneous metabolic pathway subtypes with different metabolic profiles: Cluster 1, an ECM-producing subtype with upregulated glycan metabolism; Cluster 2, a hybrid subtype with partial pathway dysregulation. Cluster 3, a lipogenic subtype with upregulated lipid metabolism; These three subtypes have different prognosis, clinical features and genomic alterations. We identified key enzymes that respond to matrix stiffness and regulate lipid metabolism through bioinformatic analysis. We found long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness. ACADL is also regarded as tumor suppressor in HCC. We found that increased extracellular matrix stiffness led to activation of Yes-associated protein (YAP) and the YAP/TEA Domain transcription factor 4 (TEAD4) transcriptional complex was able to directly repress ACADL at the transcriptional level. The ACADL-dependent mechanoresponsive pathway is a potential therapeutic target for HCC treatment.

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P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice by increasing tissue stiffness

Cited by 7 publications

References 29 publications

Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review

Biophysics of Tumor Microenvironment and Cancer Metastasis - A Mini Review

Human colorectal cancer progression correlates with LOX-induced ECM stiffening

Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma

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