SHH/GLI2-TGF-β1 feedback loop between cancer cells and tumor-associated macrophages maintains epithelial-mesenchymal transition and endoplasmic reticulum homeostasis in cholangiocarcinoma

Chen, Zuxiao; Li, Haiyan; Li, Zongyan; Chen, Shaoyi; Huang, Xiaoming; Zheng, Zheyu; Qian, Xiangjun; Zhang, Lei; Long, Guojie; Xie, Jiancong; Wang, Qian; Pan, Weidong; Zhang, Dawei

doi:10.1016/j.phrs.2022.106564

Cited by 12 publications

(8 citation statements)

References 37 publications

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“…It activates fibroblasts and promotes the deposition of extracellular matrix (ECM) 12 . Accumulating evidence have demonstrated that increased expression of TGF-β1 is associated with tumor aggressiveness and poor prognosis in HCC 13 , bladder cancer 14 , breast cancer 15 , prostate cancer 16 and cholangiocarcinoma 17 . Besides that, it has been indicated that TGF-β1 deficiency leads to abnormal hematopoietic and endothelial cell differentiation and autoimmune diseases 18 .…”

Section: Tgf-β/smad Signaling Pathwaymentioning

confidence: 99%

The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis

Xin,

Cheng,

Zeng

et al. 2024

Int. J. Biol. Sci.

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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high incidence and mortality, accounting for approximately 90% of liver cancer. The development of HCC is a complex process involving the abnormal activation or inactivation of multiple signaling pathways. Transforming growth factor-β (TGF-β)/Small mothers against decapentaplegic (SMAD) signaling pathway regulates the development of HCC. TGF-β activates intracellular SMADs protein through membrane receptors, resulting in a series of biological cascades. Accumulating studies have demonstrated that TGF-β/SMAD signaling plays multiple regulatory functions in HCC. However, there is still controversy about the role of TGF-β/SMAD in HCC. Because it involves different pathogenic factors, disease stages, and cell microenvironment, as well as upstream and downstream relationships with other signaling pathways. This review will summary the regulatory mechanism of the TGF-β/SMAD signaling pathway in HCC, involving the regulation of different pathogenic factors, different disease stages, different cell populations, microenvironments, and the interaction with microRNAs. In addition, we also introduced small molecule inhibitors, therapeutic vaccines, and traditional Chinese medicine extracts based on targeting the TGF-β/SMAD signaling pathway, which will provide future research direction for HCC therapy targeting the TGF-β/SMAD signaling pathway.

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Section: Tgf-β/smad Signaling Pathwaymentioning

confidence: 99%

The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis

Xin,

Cheng,

Zeng

et al. 2024

Int. J. Biol. Sci.

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“…Additionally, it has been shown that cholangiocarcinoma cells regulate TAM polarization and TGF-β1 secretion via the paracrine SHH signaling pathway. In turn, TAMs induce growth, EMT, and ER homeostasis in cholangiocarcinoma cells via TGF-β1 [75]. Evidence in a mouse model of CCA has demonstrated that M2-polarized macrophages promote tumor growth and invasiveness through IL-10/STAT3 signaling [76].…”

Section: Tams and Tumor Cells' Cross-talkmentioning

confidence: 99%

Macrophages Orchestrate the Liver Tumor Microenvironment

Quaranta,

Ballarò,

Giannelli

2024

Cancers

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Liver cancer is one of the leading causes of cancer-related mortality. Hepatocellular carcinoma and cholangiocarcinoma are the most common types, and despite numerous advances, therapeutic options still remain poor for these cancer patients. Tumor development and progression strictly depend on a supportive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant immune cells population within a tumorigenic liver; they sustain cancer cells’ growth and invasiveness, and their presence is correlated with a poor prognosis. Furthermore, TAM cross-talk with cells and components of the TME promotes immunosuppression, a desmoplastic response, and angiogenesis. In this review, we summarize the latest advances in understanding TAM heterogeneity and function, with a particular focus on TAM modulation of the TME. We also discuss the potential of targeting macrophage subpopulations and how this is now being exploited in current clinical trials for the treatment of liver cancer.

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“…Mutual crosstalk between CSCs and TAMs has been emphasized in CCA [48][49][50][51] . The two cell types are important CCA cell contingents comprising 30% CSCs and 10% TAMs [39,52] .…”

Section: Emt Stemness and Immune Microenvironment In Cholangiocarcinomamentioning

confidence: 99%

Crosstalk between cancer cell plasticity and immune microenvironment in cholangiocarcinoma

Minini,

Pavy,

Lekbaby

et al. 2024

Hepatoma Res

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Cholangiocarcinoma (CCA) is a highly aggressive tumor of the biliary tree characterized by an intense desmoplastic tumor microenvironment (TME). To date, treatment of CCA remains challenging; tumor resection is the only curative treatment with a high recurrence probability. Besides resection, therapeutic options have moved forward with the advent of immunotherapies, but these remain limited and low effective. Our knowledge about the cellular interplays in CCA is still fragmentary. An area is currently emerging regarding the potential role of cancer cell plasticity in the genesis of an immunosuppressive microenvironment. The cancer cells’ ability to acquire stemness properties and to disseminate through an epithelial-mesenchymal transition (EMT) shape a tumor immune microenvironment that supports cancer progression by attracting immunosuppressive cells including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and by increasing the expression of inhibitory immune checkpoints such as PD-1/PD-L-1. EMT-inducing transcription factors (EMT-TF) have recently emerged as regulators of tumor immunity by creating an immunosuppressive microenvironment. This review delves into the molecular mechanisms underlying the existing links between EMT/stemness and tumor immune microenvironment, as well as the last discoveries in CCA.

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SHH/GLI2-TGF-β1 feedback loop between cancer cells and tumor-associated macrophages maintains epithelial-mesenchymal transition and endoplasmic reticulum homeostasis in cholangiocarcinoma

Cited by 12 publications

References 37 publications

The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis

The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis

Macrophages Orchestrate the Liver Tumor Microenvironment

Crosstalk between cancer cell plasticity and immune microenvironment in cholangiocarcinoma

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