Thrombomodulin expression impacts the recurrence and long‐term survival in pancreatic cancer

Sugano, Hiroshi; Shirai, Yoshio; Sato, Shun; Hamatani, Shigeharu; Hamura, Ryoga; Taniai, Tomohiko; Horiuchi, Takashi; Gocho, Takeshi; Eto, Ken; Ikegami, Toru

doi:10.1002/ags3.12447

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…TM plays different physical roles. Different domains of TM have been shown to be related in cancer initiation, progression, and different clinical outcomes (Esmon, 2003; Furukawa et al, 2022; Kajioka et al, 2021; Shirai et al, 2017; Sugano et al, 2021; Watt et al, 2020; Yang et al, 2017; Zheng et al, 2016). Recombinant TM has been utilized as an adjuvant chemotherapeutic agent in cancer.…”

Section: Discussionmentioning

confidence: 99%

“…However, higher ITGB3 levels were significantly correlated with poor relapse-free survival (HR = 1.65, p = .006). TM is an endothelial thrombin receptor which is expressed in many cancers (Hanly et al, 2005;Sugano et al, 2021;Tezuka et al, 1995;Zhang et al, 1998). It has been shown to play a tumor-suppressor role by harnessing cancer cell proliferation, invasion, and metastasis (Furukawa et al, 2022;Hanly et al, 2005).…”

Section: Itgb3 Levels Were Correlated To the Outcome Of Tnbc Patientsmentioning

confidence: 99%

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The role of thrombomodulin in modulating ITGB3 expression and its implications for triple‐negative breast cancer progression

Chang,

Prince,

Wei

et al. 2023

Cell Biology International

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Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer (BC) compared to other BC subtypes in clinical settings. Currently, there are no effective therapeutic strategies for TNBC treatment. Therefore, there is an urgent need to identify suitable biomarkers or therapeutic targets for TNBC patients. Thrombomodulin (TM) plays a role in cancer progression and metastasis in many different cancers. However, the role of TM in TNBC is not yet fully understood. First, silenced‐TM in MDA‐MB‐231 cells caused an increase in proliferative and metastatic activity. In contrast, overexpression of TM in Hs578T cells caused a reduction in proliferation, invasion, and migration rate. Using RNA‐seq analysis, we found that Integrin beta 3 (ITGB3) expression may be a downstream target of TM. Furthermore, we found an increase in ITGB3 levels in TM‐KD cells by QPCR and western blot analysis but a decrease in ITGB3 levels in TM‐overexpressing cells. We found phospho‐smad2/3 levels were increased in TM‐KD cells but decreased in TM‐overexpressing cells. This implies that TM negatively regulates ITGB3 levels through the activation of the smad2/3 pathway. Silencing ITGB3 in TM‐KD cells caused a decrease in proliferation and migration. Finally, we found that higher ITGB3 levels were correlated with poor overall survival and relapse‐free survival in patients with TNBC. Our results indicated a novel regulatory relationship between TM and ITGB3 in TNBC.

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Section: Discussionmentioning

confidence: 99%

Section: Itgb3 Levels Were Correlated To the Outcome Of Tnbc Patientsmentioning

confidence: 99%

The role of thrombomodulin in modulating ITGB3 expression and its implications for triple‐negative breast cancer progression

Chang,

Prince,

Wei

et al. 2023

Cell Biology International

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“…Unlike CD93 and CLEC14a but like CD248, expression of TM on tumor cells themselves seems to carry more relevancy to cancer biology than angiogenesis. Importantly, unlike its group XIV relatives, TM expression appears to have a protective or anti-tumorigenic effect in several solid organ malignancies—higher expression of TM in a host of cancers such as lung adenocarcinoma, invasive breast carcinoma, oral squamous cell carcinoma (SCC) and esophageal SCC, HCC, CRC, and PDAC has been correlated with less aggressive tumors and improved patient survival [ 80 – 83 ]. Soluble TM also has been shown to have role in cancer progression, but in contrast to membrane bound TM, soluble forms seem to be upregulated in advanced cancer likely due to increased shedding from cancer cells themselves [ 84 , 85 ].…”

Section: Introductionmentioning

confidence: 99%

Group XIV C-type lectins: emerging targets in tumor angiogenesis

Yee,

Vigil,

Sun

et al. 2024

Angiogenesis

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C-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology. Recently, group XIV CTLDs have been shown to play significant roles in cancer progression, namely tumor angiogenesis and metastatic dissemination. Interest in therapeutically targeting tumor vasculature is increasing and the search for novel angiogenic targets is ongoing. Group XIV CTLDs have emerged as key moderators of tumor angiogenesis and metastasis, thus offering substantial therapeutic promise for the clinic. Herein, we review our current knowledge of group XIV CTLDs, discuss each’s role in malignancy and associated potential therapeutic avenues, briefly discuss group XIV CTLDs in the context of two other relevant lectin families, and offer future direction in further elucidating mechanisms by which these proteins function and facilitate tumor growth.

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Role of Fibrinolytic Mechanisms in Breast Cancer Diagnosis, Prognosis, and Treatment

Qazi

Akhtar

Saeed

et al. 2022

Breast Cancer: From Bench to Personalized Medicine

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Thrombomodulin expression impacts the recurrence and long‐term survival in pancreatic cancer

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 4 publications

References 28 publications

The role of thrombomodulin in modulating ITGB3 expression and its implications for triple‐negative breast cancer progression

The role of thrombomodulin in modulating ITGB3 expression and its implications for triple‐negative breast cancer progression

Group XIV C-type lectins: emerging targets in tumor angiogenesis

Role of Fibrinolytic Mechanisms in Breast Cancer Diagnosis, Prognosis, and Treatment

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