Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer

Koivusalo, Saara; Schmidt, Anette; Manninen, Aki; Wenta, Tomasz

doi:10.3390/cancers15010149

Cited by 4 publications

(2 citation statements)

References 180 publications

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“…Cells were fixed with 4% PFA in PBS+/+ (PBS with 0.9 mM CaCl 2 and 0.5 mM MgCl 2 ) for 15 min at room temperature for slide and 30 min for IBIDI. Immunofluorescence staining was performed as previously described 7 . Confocal images were acquired with the Zeiss LSM 780 laser scanning confocal microscope using 40x Plan-Apochromat objective (NA = 1.4) or with Olympus FluoView FV100 confocal microscope using 20x and 40x objective (NA = 0.75).…”

Section: Methodsmentioning

confidence: 99%

“…[3,4] Loss of PCa cell polarity coincides with reduced expression of laminin, a central basement membrane component, and disassembly of 𝛼6𝛽4-integrin-mediated hemidesmosomal laminin adhesions. [5][6][7] PCa progression is associated with increased expression of collagen that is the major constituent of stromal ECM. 𝛼1𝛽1and 𝛼2𝛽1-integrins are collagen-binding integrins that may also interact with laminins and are expressed in prostate epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression

Cruz,

Zhang,

Devarajan

et al. 2024

Advanced Science

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The extracellular matrix (ECM) undergoes substantial changes during prostate cancer (PCa) progression, thereby regulating PCa growth and invasion. Herein, a meta‐analysis of multiple PCa cohorts is performed which revealed that downregulation or genomic loss of ITGA1 and ITGA2 integrin genes is associated with tumor progression and worse prognosis. Genomic deletion of both ITGA1 and ITGA2 activated epithelial‐to‐mesenchymal transition (EMT) in benign prostate epithelial cells, thereby enhancing their invasive potential in vitro and converting them into tumorigenic cells in vivo. Mechanistically, EMT is induced by enhanced secretion and autocrine activation of TGFβ1 and nuclear targeting of YAP1. An unbiased genome‐wide co‐expression analysis of large PCa cohort datasets identified the transcription factor TEAD1 as a key regulator of ITGA1 and ITGA2 expression in PCa cells while TEAD1 loss phenocopied the dual loss of α1‐ and α2‐integrins in vitro and in vivo. Remarkably, clinical data analysis revealed that TEAD1 downregulation or genomic loss is associated with aggressive PCa and together with low ITGA1 and ITGA2 expression synergistically impacted PCa prognosis and progression. This study thus demonstrated that loss of α1‐ and α2‐integrins, either via deletion/inactivation of the ITGA1/ITGA2 locus or via loss of TEAD1, contributes to PCa progression by inducing TGFβ1‐driven EMT.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression

Cruz,

Zhang,

Devarajan

et al. 2024

Advanced Science

Self Cite

View full text Add to dashboard Cite

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Plectin: Dual Participation in Tumor Progression

Wang,

Luo

et al. 2024

Biomolecules

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The plectin gene can encode a cytoskeletal linking protein, plectin, known for its interaction with three critical components of the cellular cytoskeleton: intermediate filaments, microtubules, and actin filaments. In recent years, more and more studies have reported that plectin is closely related to tumorigenesis and development, exhibiting both tumor-suppressive and tumor-promoting functions. Here, we first introduce the molecular structure and function of plectin, and then we summarize the current understanding of the crucial role of plectin in cancer progression. Finally, we also discuss the possible reasons for the different roles of plectin expression in various types of cancer and highlight the double-edged sword role of plectin in tumor progression. The review aims to deepen the comprehensive understanding of plectin’s role in cancer and further help to develop novel therapeutic strategies and drug targets.

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The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery

Samaržija

2023

Biomedicines

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Prostate cancer is among the top five cancer types according to incidence and mortality. One of the main obstacles in prostate cancer management is the inability to foresee its course, which ranges from slow growth throughout years that requires minimum or no intervention to highly aggressive disease that spreads quickly and resists treatment. Therefore, it is not surprising that numerous studies have attempted to find biomarkers of prostate cancer occurrence, risk stratification, therapy response, and patient outcome. However, only a few prostate cancer biomarkers are used in clinics, which shows how difficult it is to find a novel biomarker. Cell adhesion to the extracellular matrix (ECM) through integrins is among the essential processes that govern its fate. Upon activation and ligation, integrins form multi-protein intracellular structures called integrin adhesion complexes (IACs). In this review article, the focus is put on the biomarker potential of the ECM- and IAC-related molecules stemming from both body fluids and prostate cancer tissue. The processes that they are involved in, such as tumor stiffening, bone turnover, and communication via exosomes, and their biomarker potential are also reviewed.

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Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer

Cited by 4 publications

References 180 publications

Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression

Dampened Regulatory Circuitry of TEAD1/ITGA1/ITGA2 Promotes TGFβ1 Signaling to Orchestrate Prostate Cancer Progression

Plectin: Dual Participation in Tumor Progression

The Potential of Extracellular Matrix- and Integrin Adhesion Complex-Related Molecules for Prostate Cancer Biomarker Discovery

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