Connective tissue growth factor expression hints at aggressive nature of colorectal cancer

Bhat, Ishrat Parveiz; Rather, Tahseen Bilal; Maqbool, Irfan; Rashid, Gowhar; Akhtar, Kulsum; Bhat, Gulzar Ahmad; Parray, Fazl Q.; Besina, Syed; Khan, Ishrat Younas; Kazi, Mohsin; Hussain, Muhammad Delwar; Mudassar, Syed

doi:10.3748/wjg.v28.i5.547

Cited by 2 publications

(1 citation statement)

References 31 publications

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“…CCN2 expression is significantly elevated in colorectal carcinoma tumor specimens compared to their paired normal specimens (Bhat et al 2022). Higher CCN2 protein expression levels showed a significant association with smoking, staging, tumor grade, invasion depth, necrosis of tumor tissue, and both lymphovascular and perineural invasion.…”

Section: Introductionmentioning

confidence: 99%

CCN proteins: opportunities for clinical studies—a personal perspective

Yeger

2023

J. Cell Commun. Signal.

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The diverse members of the CCN family now designated as CCN1(CYR61), CCN2 (CTGF), CCN3(NOV), CCN4(WISP1), CCN5(WISP2), CCN6(WISP3) are a conserved matricellular family of proteins exhibiting a spectrum of functional properties throughout all organs in the body. Interaction with cell membrane receptors such as integrins trigger intracellular signaling pathways. Proteolytically cleaved fragments (constituting the active domains) can be transported to the nucleus and perform transcriptional relevant functional activities. Notably, as also found in other protein families some members act opposite to others creating a system of functionally relevant checks and balances. It has become apparent that these proteins are secreted into the circulation, are quantifiable, and can serve as disease biomarkers. How they might also serve as homeostatic regulators is just becoming appreciated. In this review I have attempted to highlight the most recent evidence under the subcategories of cancer and non‐cancer relevant that could lead to potential therapeutic approaches or ideas that can be factored into clinical advances. I have added my own personal perspective on feasibility.

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Section: Introductionmentioning

confidence: 99%

CCN proteins: opportunities for clinical studies—a personal perspective

Yeger

2023

J. Cell Commun. Signal.

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Combined High—Throughput Proteomics and Random Forest Machine-Learning Approach Differentiates and Classifies Metabolic, Immune, Signaling and ECM Intra-Tumor Heterogeneity of Colorectal Cancer

Contini,

Manconi,

Olianas

et al. 2024

Cells

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Colorectal cancer (CRC) is a frequent, worldwide tumor described for its huge complexity, including inter-/intra-heterogeneity and tumor microenvironment (TME) variability. Intra-tumor heterogeneity and its connections with metabolic reprogramming and epithelial–mesenchymal transition (EMT) were investigated with explorative shotgun proteomics complemented by a Random Forest (RF) machine-learning approach. Deep and superficial tumor regions and distant-site non-tumor samples from the same patients (n = 16) were analyzed. Among the 2009 proteins analyzed, 91 proteins, including 23 novel potential CRC hallmarks, showed significant quantitative changes. In addition, a 98.4% accurate classification of the three analyzed tissues was obtained by RF using a set of 21 proteins. Subunit E1 of 2-oxoglutarate dehydrogenase (OGDH-E1) was the best classifying factor for the superficial tumor region, while sorting nexin-18 and coatomer-beta protein (beta-COP), implicated in protein trafficking, classified the deep region. Down- and up-regulations of metabolic checkpoints involved different proteins in superficial and deep tumors. Analogously to immune checkpoints affecting the TME, cytoskeleton and extracellular matrix (ECM) dynamics were crucial for EMT. Galectin-3, basigin, S100A9, and fibronectin involved in TME–CRC–ECM crosstalk were found to be differently variated in both tumor regions. Different metabolic strategies appeared to be adopted by the two CRC regions to uncouple the Krebs cycle and cytosolic glucose metabolism, promote lipogenesis, promote amino acid synthesis, down-regulate bioenergetics in mitochondria, and up-regulate oxidative stress. Finally, correlations with the Dukes stage and budding supported the finding of novel potential CRC hallmarks and therapeutic targets.

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Connective tissue growth factor expression hints at aggressive nature of colorectal cancer

Cited by 2 publications

References 31 publications

CCN proteins: opportunities for clinical studies—a personal perspective

CCN proteins: opportunities for clinical studies—a personal perspective

Combined High—Throughput Proteomics and Random Forest Machine-Learning Approach Differentiates and Classifies Metabolic, Immune, Signaling and ECM Intra-Tumor Heterogeneity of Colorectal Cancer

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