The Multifaceted Role of TGF-β in Gastrointestinal Tumors

Sabbadini, Fabio; Bertolini, Monica; Matteis, Serena De; Mangiameli, Domenico; Contarelli, Serena; Pietrobono, Silvia; Melisi, Davide

doi:10.3390/cancers13163960

Cited by 28 publications

(25 citation statements)

References 220 publications

(215 reference statements)

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“…TGF is a key regulator of cell growth and apoptosis in PC[ 141 ] , and alterations in its signaling have been associated with early and advanced stages of gastrointestinal cancer, especially in PC[ 142 ]. Elevated TGFβ was not detected in pancreatic lesions by some authors[ 143 ], whereas TGFβ-1, TGFβ-2, and TGFβ-3 isoforms were correlated with more advanced cancer PC stage and worse survival outcomes[ 144 ].…”

Section: Inflammatory and Growth Factorsmentioning

confidence: 99%

Liquid biopsy approach to pancreatic cancer

Perales

Torres

Jiménez-Luna

et al. 2021

WJGO

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Pancreatic cancer (PC) continues to pose a major clinical challenge. There has been little improvement in patient survival over the past few decades, and it is projected to become the second leading cause of cancer mortality by 2030. The dismal 5-year survival rate of less than 10% after the diagnosis is attributable to the lack of early symptoms, the absence of specific biomarkers for an early diagnosis, and the inadequacy of available chemotherapies. Most patients are diagnosed when the disease has already metastasized and cannot be treated. Cancer interception is vital, actively intervening in the malignization process before the development of a full-blown advanced tumor. An early diagnosis of PC has a dramatic impact on the survival of patients, and improved techniques are urgently needed to detect and evaluate this disease at an early stage. It is difficult to obtain tissue biopsies from the pancreas due to its anatomical position; however, liquid biopsies are readily available and can provide useful information for the diagnosis, prognosis, stratification, and follow-up of patients with PC and for the design of individually tailored treatments. The aim of this review was to provide an update of the latest advances in knowledge on the application of carbohydrates, proteins, cell-free nucleic acids, circulating tumor cells, metabolome compounds, exosomes, and platelets in blood as potential biomarkers for PC, focusing on their clinical relevance and potential for improving patient outcomes.

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Section: Inflammatory and Growth Factorsmentioning

confidence: 99%

Liquid biopsy approach to pancreatic cancer

Perales

Torres

Jiménez-Luna

et al. 2021

WJGO

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“…In the context of liver physiology, TGF-β exhibits potent cytostatic and proapoptotic effects in normal and premalignant hepatocytes, as well as early stage liver cancer cells [ 10 , 11 ]. However, during the course of HCC progression, TGF-β switches to a pro-tumorigenic signal within the tumor itself and in the tumor stroma, inducing aggressive phenotypes, such as cancer cell proliferation, epithelial–mesenchymal transition (EMT), as well as tumor microenvironment (TME) remodeling and immune evasion of cancer cells [ 12 ]. In this article, we thoroughly review the dichotomous functions of TGF-β signaling in HCC and outline the implications of its biphasic nature for therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

The Bright and the Dark Side of TGF-β Signaling in Hepatocellular Carcinoma: Mechanisms, Dysregulation, and Therapeutic Implications

Gungor

Uysal

Şentürk

2022

Cancers

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Hepatocellular carcinoma (HCC) is associated with genetic and nongenetic aberrations that impact multiple genes and pathways, including the frequently dysregulated transforming growth factor β (TGF-β) signaling pathway. The regulatory cytokine TGF-β and its signaling effectors govern a broad spectrum of spatiotemporally regulated molecular and cellular responses, yet paradoxically have dual and opposing roles in HCC progression. In the early stages of tumorigenesis, TGF-β signaling enforces profound tumor-suppressive effects, primarily by inducing cell cycle arrest, cellular senescence, autophagy, and apoptosis. However, as the tumor advances in malignant progression, TGF-β functionally switches to a pro-tumorigenic signal, eliciting aggressive tumor traits, such as epithelial–mesenchymal transition, tumor microenvironment remodeling, and immune evasion of cancer cells. On this account, the inhibition of TGF-β signaling is recognized as a promising therapeutic strategy for advanced HCC. In this review, we evaluate the functions and mechanisms of TGF-β signaling and relate its complex and pleiotropic biology to HCC pathophysiology, attempting to provide a detailed perspective on the molecular determinants underlying its functional diversion. We also address the therapeutic implications of the dichotomous nature of TGF-β signaling and highlight the rationale for targeting this pathway for HCC treatment, alone or in combination with other agents.

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“…На ранних стадиях онкогенеза TGF-β действует как опухолевый супрессор, вызывая цитостатический эффект и апоптоз в нормальных и предзлокачественных клетках. Однако после развития опухоли TGF-β функционирует как промотор опухоли, запускающий переход эпителия в мезенхиму, что приводит к повышенной инвазивности и развитию метастазов [33]. TGF-β также поддерживает прогрессирование опухоли, стимулируя фиброз, ангиогенез и подавление иммунитета [26,33,56] Парадоксальное влияние передачи сигналов TGF-β в различных опухолях вызывает опасения, что передача сигналов против TGF-β может привести к плохому прогнозу из-за его роли супрессора опухолей.…”

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“…Однако после развития опухоли TGF-β функционирует как промотор опухоли, запускающий переход эпителия в мезенхиму, что приводит к повышенной инвазивности и развитию метастазов [33]. TGF-β также поддерживает прогрессирование опухоли, стимулируя фиброз, ангиогенез и подавление иммунитета [26,33,56] Парадоксальное влияние передачи сигналов TGF-β в различных опухолях вызывает опасения, что передача сигналов против TGF-β может привести к плохому прогнозу из-за его роли супрессора опухолей. Эта проблема задерживает развитие ингибиторов TGF-β в качестве терапевтических средств [29].…”

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“…Эта проблема задерживает развитие ингибиторов TGF-β в качестве терапевтических средств [29]. Эта дихотомия в функциях TGF-β остается фундаментальным препятствием на пути эффективного воздействия на сигнальный путь TGF-β для лечения рака человека [33].…”

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Role of transforming growth factor beta in tumor process

Кукес¹,

Prokofiev²,

Parfenova³

et al. 2021

Humans and their Health

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The study and application of representatives of the transforming growth factor-beta (TGF-β) family in practical medicine remains an urgent task at the present time. A more detailed study of the properties and activity of proteins related to TGF-β opens up new possibilities in the treatment and diagnosis of diseases associated with skeletal muscles, female reproductive system, oncology and the cardiovascular system, as well as in the development of drugs based on them. This work examines the role of TGF-β in tumor development and the potential of this protein as a therapeutic target, as well as the signaling pathway, various marker proteins, and various types of receptors involved in this process. During tumor development, TGF-β uses two pathways: the classic SMAD-dependent pathway and the non-SMAD-dependent pathway. In the early stages of tumorigenesis, TGF-β acts as a tumor suppressor, causing a cytostatic effect and apoptosis in normal and pre-malignant cells. However, after tumor development, TGF-β functions as a tumor promoter, triggering the transition of the epithelium to the mesenchyme, which leads to increased invasiveness and the development of metastases. The role of TGF-β in oncogenesis in various organ systems has been studied, including in breast, colon, stomach, hepatocellular carcinoma, thyroid cancer, etc. Specifically, TGF-β1 causes a wide range of different physiological reactions, regulates development, differentiation, carcinogenesis and tumor progression of epithelial cells, has multiple effects on the entire process of hematopoiesis. Directions for the creation of drugs for the treatment of tumors targeting TGF-β are presented.

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The Multifaceted Role of TGF-β in Gastrointestinal Tumors

Cited by 28 publications

References 220 publications

Liquid biopsy approach to pancreatic cancer

Liquid biopsy approach to pancreatic cancer

The Bright and the Dark Side of TGF-β Signaling in Hepatocellular Carcinoma: Mechanisms, Dysregulation, and Therapeutic Implications

Role of transforming growth factor beta in tumor process

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