Interplay Between LOX Enzymes and Integrins in the Tumor Microenvironment

Amendola, Pier Giorgio; Reuten, Raphael; Erler, Janine T.

doi:10.3390/cancers11050729

Cited by 59 publications

(64 citation statements)

References 149 publications

(198 reference statements)

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“…Contrasting these observations, LOX was reported to have tumour suppressive effects in human OSA cell lines, although this capacity was not tested in vivo [ 104 ]. The results of this study in OSA are in disagreement to the well documented role of LOX in ECM remodelling in epithelial malignancies, leading to increased integrin signalling, and metastatic colonisation [ 105 , 106 ]. Similar involvement of LOX in tumour dissemination was reported for undifferentiated pleomorphic sarcoma (UPS), where HIF1 alpha promoted the expression of PLOD2, and PLOD2 inhibition led to a decrease in collagen deposition, organisation and maturation, and a decrease in lung metastases [ 107 ].…”

Section: Mechanotransduction In Osteosarcoma and Promising Targetacontrasting

confidence: 99%

Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

Luu

Viloria-Petit

2020

IJMS

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Mechanotransduction is the process in which cells can convert extracellular mechanical stimuli into biochemical changes within a cell. While this a normal process for physiological development and function in many organ systems, tumour cells can exploit this process to promote tumour progression. Here we summarise the current state of knowledge of mechanotransduction in osteosarcoma (OSA), the most common primary bone tumour, referencing both human and canine models and other similar mesenchymal malignancies (e.g., Ewing sarcoma). Specifically, we discuss the mechanical properties of OSA cells, the pathways that these cells utilise to respond to external mechanical cues, and mechanotransduction-targeting strategies tested in OSA so far. We point out gaps in the literature and propose avenues to address them. Understanding how the physical microenvironment influences cell signalling and behaviour will lead to the improved design of strategies to target the mechanical vulnerabilities of OSA cells.

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Section: Mechanotransduction In Osteosarcoma and Promising Targetacontrasting

confidence: 99%

Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

Luu

Viloria-Petit

2020

IJMS

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“…This ECM remodelling activity is critical for creating a structurally integrated ECM network and providing tensile strength to tissues. Increased expression and activity of all LOX family members is strongly implicated in cancer progression (for more details, see Refs ).…”

Section: Extracellular Matrix Composition and Dynamicsmentioning

confidence: 99%

Framing cancer progression: influence of the organ‐ and tumour‐specific matrisome

Rafaeva

Erler

2020

The FEBS Journal

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The extracellular matrix (ECM) plays a crucial role in regulating organ homeostasis. It provides mechanical and biochemical cues directing cellular behaviour and, therefore, has control over the progression of diseases such as cancer. Recent efforts have greatly enhanced our knowledge of the protein composition of the ECM and its regulators, the so-called matrisome, in healthy and cancerous tissues; yet, an overview of the common signatures and organ-specific ECM in cancer is missing. Here, we address this by taking a detailed approach to review why cancer grows in certain organs, and focus on the influence of the matrisome at primary and metastatic tumour sites. Our in-depth and comprehensive review of the current literature and general understanding identifies important commonalities and distinctions, providing insight into the biology of metastasis, which could pave the way to improve future diagnostics and therapies.

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“…oxidase which has been implicated in promoting cancer progression and metastasis [60][61][62][63][64]. EMIL1 is an extracellular matrix glycoprotein that has been identified in both primary and metastatic colon tumours [65].…”

Section: Plos Onementioning

confidence: 99%

SWATH-MS based proteomic profiling of pancreatic ductal adenocarcinoma tumours reveals the interplay between the extracellular matrix and related intracellular pathways

et al. 2020

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Pancreatic cancer accounts for 2.8% of new cancer cases worldwide and is projected to become the second leading cause of cancer-related deaths by 2030. Patients of African ancestry appear to be at an increased risk for pancreatic ductal adenocarcinoma (PDAC), with more severe disease and outcomes. The purpose of this study was to map the proteomic and genomic landscape of a cohort of PDAC patients of African ancestry. Thirty tissues (15 tumours and 15 normal adjacent tissues) were obtained from consenting South African PDAC patients. Optimisation of the sample preparation method allowed for the simultaneous extraction of high-purity protein and DNA for SWATH-MS and OncoArray SNV analyses. We quantified 3402 proteins with 49 upregulated and 35 downregulated proteins at a minimum 2.1 fold change and FDR adjusted p-value (q-value) � 0.01 when comparing tumour to normal adjacent tissue. Many of the upregulated proteins in the tumour samples are involved in extracellular matrix formation (ECM) and related intracellular pathways. In addition, proteins such as EMIL1, KBTB2, and ZCCHV involved in the regulation of ECM proteins were observed to be dysregulated in pancreatic tumours. Downregulation of pathways involved in oxygen and carbon dioxide transport were observed. Genotype data showed missense mutations in some upregulated proteins, such as MYPN, ESTY2 and SERPINB8. Approximately 11% of the dysregulated proteins, including ISLR, BP1, PTK7 and OLFL3, were predicted to be secretory proteins. These findings help in further elucidating the biology of PDAC and may aid in identifying future plausible markers for the disease.

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Interplay Between LOX Enzymes and Integrins in the Tumor Microenvironment

Cited by 59 publications

References 149 publications

Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

Framing cancer progression: influence of the organ‐ and tumour‐specific matrisome

SWATH-MS based proteomic profiling of pancreatic ductal adenocarcinoma tumours reveals the interplay between the extracellular matrix and related intracellular pathways

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