Association between focal adhesion kinase and matrix metalloproteinase-9 expression in prostate adenocarcinoma and their influence on the progression of prostatic adenocarcinoma

Atılgan, Alev Ok; Ozdemır, B. Handan; Akçay, Eda Yılmaz; Tepeoğlu, Merıh; Börcek, Pelin; Dirim, Ayhan

doi:10.1016/j.anndiagpath.2020.151480

Cited by 10 publications

(7 citation statements)

References 16 publications

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“…These mutual confirmation result indicated boosting cell proliferation, cell movement and metabolism in the development of PCa cell. These changes were reported in other cancers and suggested the reliability of our screening methods (45)(46)(47)(48)(49)(50).…”

Section: Discussionsupporting

confidence: 78%

Identification of candidate hub genes correlated with the pathogenesis, diagnosis, and prognosis of prostate cancer by integrated bioinformatics analysis

Wei¹,

Liang²,

Anderson³

et al. 2022

Transl Cancer Res TCR

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Background: Prostate cancer (PCa) has the second highest morbidity and mortality rates in men.Concurrently, novel diagnostic and prognostic biomarkers of PCa remain crucial.Methods: This study utilized integrated bioinformatics method to identify and validate the potential hub genes with high diagnostic and prognostic value for PCa.Results: Four Gene Expression Omnibus (GEO) datasets including 123 PCa samples and 76 normal samples were screened and a total of 368 differentially expressed genes (DEGs), including 120 up-regulated DEGs and 248 down-regulated DEGs, were identified. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were majorly enriched in focal adhesion, chemical carcinogenesis, drug metabolism, and cytochrome P450 pathways. Then, 11 hub genes were identified from the protein-protein interaction (PPI) network of the DEGs; 7 of the 11 genes showed the ability of distinguishing PCa from normal prostate based on receiver operating characteristic (ROC) curve analysis. And 5 of the 11 genes were correlated with clinical attributes. Lower CAV1, KRT5, SNAI2 and MYLK expression level were associated with higer Gleason score, advanced pathological T stage and N stage. Lower KRT5 and MYLK expression level were significantly correlated with poor disease-free survival, and lower KRT5 and PTGS2 expression level were significantly related to biochemical recurrence (BCR) status of PCa patients. Conclusions:In conclusion, CAV1, KRT5, SNAI2, and MYLK show potential clinical diagnostic and prognostic value and could be used as novel candidate biomarkers and therapeutic targets for PCa.

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Section: Discussionsupporting

confidence: 78%

Identification of candidate hub genes correlated with the pathogenesis, diagnosis, and prognosis of prostate cancer by integrated bioinformatics analysis

Wei¹,

Liang²,

Anderson³

et al. 2022

Transl Cancer Res TCR

View full text Add to dashboard Cite

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“…MMP-9 plays a key role in cancer development and progression, which is related to tumor metastasis in many types of malignancies [10][11][12][13][14]. Moreover, deletion of the MMP-9 gene has been reported to delay the tumor onset or suppressed tumor progression in many genetically engineered mouse models of cancers [15][16][17][18][19].…”

Section: Discussionmentioning

confidence: 99%

MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway

Yin

Chen

et al. 2021

Analytical Cellular Pathology

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Oral squamous cell carcinoma (OSCC) is one of the most common types of cancers in developing countries. A major contributor to the high mortality rate of OSCC is the tendency of oral cancer cells to metastasize to lymph nodes around the head and neck during the early stages of cancer development. Matrix metalloproteinase 9 (MMP-9), an endopeptidase, can degrade the extracellular matrix and basement membrane and plays a key role in tumor invasion and metastasis. In vitro, cell migration ability was conducted by scratching assays. We also investigated the interaction abilities between OSCC cells and vascular endothelial cells (ECs) by an adhesion assay and transendothelial migration assay. And we established a BALB/c nude mouse tongue-xenografted metastasis model to investigate the role of MMP-9 and explore its potential underlying mechanism in OSCC growth, lymph node metastasis, and angiogenesis in vivo. The results showed that knockdown of MMP-9 could significantly suppress OSCC cell migration, proliferation, interactions between endothelial cells, xenografted tumor growth, and angiogenesis and simultaneously markedly inhibited OSCC cell metastasis to mouse lymphonodi cervicales superficiales, axillary lymph nodes, and even distant inguinal lymph nodes. Mechanistic studies revealed that knockdown of MMP-9 also led to a decreased expression of RhoC, Src, and F-actin by RT-PCR, western blotting, and immunohistochemistry. And the bioinformatic analysis showed that MMP-9, RhoC, and Src mRNA expression was positively and linearly correlated in OSCC on TCGA database. Together, our findings indicated that MMP-9 plays a very important role in OSCC growth, migration, angiogenesis, and lymph node metastasis, and its potential mechanism may be mediated by RhoC and Src gene expression.

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“…[130] In the progression of prostate adenocarcinoma, overexpression of FAK was seen in combination with MMP9, but was observed in patient samples with and without PNI. [131] Stress-induced phosphoprotein 1 (STIP1) was reported to activate the FAK/AKT/MMP signaling axis to promote pancreatic cancer. [132] Similarly, CX3CR1-positive pancreatic cancer cells promoted nerve-cancer cell adhesion by activating GPCRs via FAK and β1 integrins to promote PNI.…”

Section: Focal Adhesion Kinase (Fak)mentioning

confidence: 99%

The Role of ECM Remodeling, EMT, and Adhesion Molecules in Cancerous Neural Invasion: Changing Perspectives

Mukherjee

Wai

et al. 2022

Advanced Biology

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the nerve, is often used synonymously with the term PNI. It is important to differentiate between these two terms as the former can be determined using imaging techniques as it is apparent both clinically and radiologically whereas the latter is more of a histological diagnosis. [4,5] The presence of PNI in malignant neoplasms serves as a marker for poor clinical prognosis and higher mortality rate among patients. PNI is most commonly detected in the aggressive pancreatic, prostate, head and neck, colorectal and gastric cancers. [6] Importantly, in some of these cancers, PNI is the only method of metastasis and it can exist independently without vascular and lymphatic invasion. [2,7] In head and neck, the prevalence of PNI varies between 25-80% when compared to non-PNI cases, whereas in pancreatic cancer, 90% of patients exhibit PNI. [8,9] Furthermore, multiple population-based studies carried out over the years have reported no significant difference in the development of PNI based on age, gender, ethnicity/race or other demographic risk factors like smoking history. [10,11,12] Knowledge of the structure and composition of the nerve and its perineural niche is integral to understanding PNI. The peripheral nerves are primarily composed of Schwann cells, fibroblasts, blood vessels along with axon bundles. The Schwann cells are essential for the maintenance of the axons as well as for the production of myelin in the peripheral nervous system. [13] The innermost endoneurium is composed of the extracellular matrix (ECM), fibroblasts and collagen. It is a delicate layer of connective tissue which wraps around the axon and capillaries. The axons are supported and protected by endoneurial cells which are found in this layer. [14] The perineurium has one or more layers of flat epithelial-like cells which group the axons and endoneurium into fascicles. The presence of tight and adherens junctions (AJs) in the epithelial layer adds to the robustness of this layer thereby providing a permeable, but selective barrier between the surrounding axons and tissues. [15] And finally, the outermost epineurium consists of a dense connective tissue layer composed of elastin fibers and collagen which surround the entire nerve bundle. [16] Numerous blood vessels can also be found in this layer as they serve as the vascular supply to the nerve. Based on the structure of the nerve, Leibig et al. [17] combined past and present definitions and defined PNI as the presence of cancer cells along the nerves Perineural invasion (PNI) refers to the cancerous invasion of nerves. It provides an alternative route for metastatic invasion and can exist independently in the absence of lymphatic or vascular invasion.It is a prominent characteristic of specific aggressive malignancies where it correlates with poor prognosis. The clinical significance of PNI is widely recognized despite a lack of understanding of the molecular mechanisms underlying its pathogenesis. The interaction between the nerve and the cancer cells is the most pivotal PNI step which...

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Association between focal adhesion kinase and matrix metalloproteinase-9 expression in prostate adenocarcinoma and their influence on the progression of prostatic adenocarcinoma

Cited by 10 publications

References 16 publications

Identification of candidate hub genes correlated with the pathogenesis, diagnosis, and prognosis of prostate cancer by integrated bioinformatics analysis

Identification of candidate hub genes correlated with the pathogenesis, diagnosis, and prognosis of prostate cancer by integrated bioinformatics analysis

MMP-9 Knockdown Inhibits Oral Squamous Cell Carcinoma Lymph Node Metastasis in the Nude Mouse Tongue-Xenografted Model through the RhoC/Src Pathway

The Role of ECM Remodeling, EMT, and Adhesion Molecules in Cancerous Neural Invasion: Changing Perspectives

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