Matricellular proteins in intrahepatic cholangiocarcinoma

Sirica, Alphonse E.

doi:10.1016/bs.acr.2022.01.010

Cited by 12 publications

(8 citation statements)

References 137 publications

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“…We further narrowed down the potential target cargo proteins by exploring their expression profiles and prognostic value. OPN, a tumor‐associated ECM protein, attracted our attention because its profile was similar to that of RAB6A 17 . Pancancer analysis showed that OPN was upregulated in 17 cancers (Supporting Information: Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…OPN, a tumor-associated ECM protein, attracted our attention because its profile was similar to that of RAB6A. 17 Pancancer analysis showed that OPN was upregulated in 17 cancers (Supporting Information: Figure S4). Pancancer analysis showed that the expression of RAB6A was positively correlated with that of OPN in multiple cancers (Supporting Information: Figure S5).…”

Section: Opn Is a Trafficking Cargo Of Rab6a In Stem-like Cellsmentioning

confidence: 99%

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RAB6A functions as a critical modulator of the stem‐like subsets in cholangiocarcinoma

Yang

Zhu

Zheng

et al. 2023

Molecular Carcinogenesis

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RAB6A is a member of RAB GTPase family and plays an important role in the targeted transport of neurotrophic receptors and inflammatory cytokines. RAB6A‐mediated secretory pathway is involved in many physiological and pathological processes. Defects in RAB6A‐mediated secretory pathway may lead to the development of many diseases, including cancer. However, its role in cholangiocarcinoma (CCA) has not yet been revealed. We explored the regulatory role of RAB6A in the stem‐like subsets of CCA. We showed that RAB6A knockdown (KD) impedes cancer stem cells (CSCs) properties and epithelial−mesenchymal transition in vitro and that suppression of RAB6A inhibits tumor growth in vivo. We screened target cargos of RAB6A in CCA cells and identified a extracellular matrix component as the target cargo. RAB6A binds directly to OPN, and RAB6A KD suppressed OPN secretion and inhibited the interaction between OPN and αV integrin receptor. Moreover, RAB6A KD inhibited the AKT signaling pathway, which is a downstream effector of the integrin receptor signaling. In addition, shRNA targeting OPN blocked endogenous expression of OPN and consequently weakened CSCs properties in RAB6A‐formed spheres. Similarly, inhibitor of AKT signaling, MK2206 also impedes oncogenic function of RAB6A in the stem‐like subsets of CCA cells. In conclusion, our findings showed that RAB6A sustains CSCs phenotype maintenance by modulating the secretion of OPN and consequentially activating the downstream AKT signaling pathway. Targeting the RAB6A/OPN axis may be an effective strategy for CCA therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Opn Is a Trafficking Cargo Of Rab6a In Stem-like Cellsmentioning

confidence: 99%

RAB6A functions as a critical modulator of the stem‐like subsets in cholangiocarcinoma

Yang

Zhu

Zheng

et al. 2023

Molecular Carcinogenesis

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“…To understand the pro-oncogenic potential of fibrosis associated with the up-regulation of aberrant ECM proteins, we conducted in vitro studies using an established cell line of human iCCA, the HuCCT-1 cells. Previous literature dealing with other tumor contexts highlighted the ability of TnC, POSTN, and OPN to regulate several core roles, which orchestrate tumorigenesis and tumor progression, such as proliferation, cell viability, migration, angiogenesis, pro-invasive pathways, and stemness induction [30]. Starting from these premises, we analyzed iCCA cell responses to in vitro treatments with these three proteins.…”

Section: Discussionmentioning

confidence: 99%

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma

Cadamuro

Sarcognato

Camerotto

et al. 2023

IJMS

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Metabolic syndrome (MetS) is a common condition closely associated with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). Recent meta-analyses show that MetS can be prodromal to intrahepatic cholangiocarcinoma (iCCA) development, a liver tumor with features of biliary differentiation characterized by dense extracellular matrix (ECM) deposition. Since ECM remodeling is a key event in the vascular complications of MetS, we aimed at evaluating whether MetS patients with iCCA present qualitative and quantitative changes in the ECM able to incite biliary tumorigenesis. In 22 iCCAs with MetS undergoing surgical resection, we found a significantly increased deposition of osteopontin (OPN), tenascin C (TnC), and periostin (POSTN) compared to the matched peritumoral areas. Moreover, OPN deposition in MetS iCCAs was also significantly increased when compared to iCCA samples without MetS (non-MetS iCCAs, n = 44). OPN, TnC, and POSTN significantly stimulated cell motility and the cancer-stem-cell-like phenotype in HuCCT-1 (human iCCA cell line). In MetS iCCAs, fibrosis distribution and components differed quantitatively and qualitatively from non-MetS iCCAs. We therefore propose overexpression of OPN as a distinctive trait of MetS iCCA. Since OPN stimulates malignant properties of iCCA cells, it may provide an interesting predictive biomarker and a putative therapeutic target in MetS patients with iCCA.

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“…Many studies indicated that the changes of extracellular matrix (ECM) in biochemistry, biomechanics, structural composition and distribution in cancers and ECM would increase rapidly in CCA. By regulating the components or key targets of the ECM, such as type III collagen and matricellular proteins, the therapeutic effect of CCA could be achieved [ 68–70 ]. Meanwhile, Yoo et al.…”

Section: Othersmentioning

confidence: 99%

Advances in targeted therapy of cholangiocarcinoma

Li,

Yu,

Zhang

et al. 2024

Annals of Medicine

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Cholangiocarcinoma (CCA) is a malignant tumor originating in the bile duct and its branching epithelium. Due to its high heterogeneity, there are no specific clinical indications at the early stage, the diagnosis is often in advanced CCA. With surgical resection, the 5-year postoperative survival rate (long-term survival rate) is very poor. The regimen of gemcitabine combined with platinum has been used as the first-line chemotherapy for advanced patients. In recent years, targeted therapy for a variety of malignant tumors has made great progress, showing good efficacy and safety in advanced CCA. However, the current targeted therapy of CCA still has many challenges, such as adverse reactions, drug resistance, and individual differences. Therefore, the researches need to further explore the targeted therapy mechanism of CCA malignancies in depth, develop more effective and safe drugs, and accurately formulate plans based on patient characteristics to further improve patient prognosis in the future. This article reviews the recent progress of targeted therapy for CCA, aiming to provide a strategy for the research and clinical work of targeted therapy for CCA.

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Matricellular proteins in intrahepatic cholangiocarcinoma

Cited by 12 publications

References 137 publications

RAB6A functions as a critical modulator of the stem‐like subsets in cholangiocarcinoma

RAB6A functions as a critical modulator of the stem‐like subsets in cholangiocarcinoma

Intrahepatic Cholangiocarcinoma Developing in Patients with Metabolic Syndrome Is Characterized by Osteopontin Overexpression in the Tumor Stroma

Advances in targeted therapy of cholangiocarcinoma

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