Proactive and reactive roles of TGF-β in cancer

Kuburich, Nick A.; Sabapathy, Thiru; Demestichas, Breanna; Maddela, Joanna; Hollander, Petra den; Mani, Sendurai A.

doi:10.1016/j.semcancer.2023.08.002

Cited by 13 publications

(5 citation statements)

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“…Some factors specific to CSCs likely enable survival following a mitotic catastrophe; these factors may involve heightened resistance to DNA damage or plasticity. 5 , 67 – 69 Likely, differentiated (i.e., non-CSCs) could also experience a mitotic catastrophe following stabilizing vimentin phosphorylation; however, these cells may not survive, while CSCs persist as multinucleated cells, similar to survivorship bias. We previously observed that stabilizing vimentin phosphorylation with FiVe1 led to vimentin collapse and mislocalization of tubulin during mitosis before the formation of multinucleated cells.…”

Section: Discussionmentioning

confidence: 99%

Stabilizing vimentin phosphorylation inhibits stem-like cell properties and metastasis of hybrid epithelial/mesenchymal carcinomas

Kuburich,

den Hollander,

Castaneda

et al. 2023

Cell Reports

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Section: Discussionmentioning

confidence: 99%

Stabilizing vimentin phosphorylation inhibits stem-like cell properties and metastasis of hybrid epithelial/mesenchymal carcinomas

Kuburich,

den Hollander,

Castaneda

et al. 2023

Cell Reports

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“…TGF-β promotes EMT, invasion, and metastasis in prostate cancer cells, while also modulating the tumor microenvironment to support angiogenesis, immune evasion, and therapy resistance. This dysregulation contributes to tumor aggressiveness and metastatic spread in prostate cancer patients [252].…”

Section: Tgf-βmentioning

confidence: 99%

Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes

Shafi,

Rajpar,

Zafar

et al. 2024

Preprint

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Background: Hepatocellular carcinoma (HCC) presents challenges due to tumor heterogeneity and therapeutic resistance. Understanding the molecular mechanisms driving heterogeneity is crucial. Key transcription factors (HNF4A, HNF1A, FOXA1/2, etc.) and signaling pathways (Wnt/β-catenin, FGF, HGF, etc.) are dysregulated in HCC. Dysregulation disrupts hepatocyte genetic programming, leading to heterogeneous cell populations. Investigating these mechanisms offers insights for targeted therapies and improving patient outcomes in HCC. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/ subscription-based journals were searched for published articles without any date restrictions, to trace the emergence of HCC heterogeneity by investigating the hepatocyte-specific genes/TFs/signaling pathways across cellular and tumor landscapes. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate HCC Heterogeneity. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: This study into hepatocellular carcinoma (HCC) revealed dysregulation of key transcription factors (TFs) and signaling pathways. Transcription factors HNF4A, HNF1A, FOXA1/2, CEBPA, GATA4/6, PROX1, SOX9, HNF6/Onecut1, and ONECUT2/HNF6β showed altered expression patterns, disrupting hepatocyte genetic programming and promoting heterogeneous cell populations in HCC. Dysregulated Wnt/β-catenin, FGF, HGF, TGF-β, and Hippo signaling pathways influenced cellular fate decisions and interactions with the tumor microenvironment, further contributing to HCC heterogeneity. Dysregulated NOTCH signaling and TBX3/18 transcription factors highlighted the complexity of HCC heterogeneity. This study points to the critical role of dysregulated TFs and signaling pathways in driving HCC heterogeneity and transdifferentiation, providing insights for targeted therapeutic interventions to improve patient outcomes. Conclusion: The decline in the gene expression of hepatocyte cell type-specific genes dysregulates the genetic programing of hepatocytes involved in cell type-specific homeostasis. The multiple roles of every gene/TF begin to manifest themselves causing the emergence of heterogeneity. The dysregulation of hepatocyte-specific genes and signaling pathways in hepatocellular carcinoma (HCC) disrupts cellular homeostasis, leading to the emergence of heterogeneity and transdifferentiation. Key transcription factors like HNF4A, HNF1A, and FOXA1/2, along with pathways such as Wnt/β-catenin and Hippo signaling, play crucial roles. This disruption sets the stage for diverse cellular phenotypes within the tumor microenvironment. Understanding these molecular mechanisms is vital for developing targeted therapeutic strategies to address HCC heterogeneity and improve patient outcomes.

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“…(2023 г.) было продемонстрировано влияние опухолеассоциированных фибробластов на индукцию эпителиально-мезенхимального перехода (ЭМП) путем секреции TGF-β, который активирует гены, кодирующие белки, необходимые для мезенхимальных функций клеток (виментин, N-кадгерин, фибронектин-1) и подавляет экспрессию белков, важных для эпителиального фенотипа (Е-кадгерин, цитокератины и ламины) [16,17] (ИЛ-10), продуцируемого опухолевыми клетками и способствующего угнетению цитотоксической активности Т-лимфоцитов, что способствует выживанию опухолевых клеток в организме [13]. Данные о влиянии В-лимфоцитов на патогенез опухоли неоднозначны -в работе Цинь Ю. и соавт.…”

Section: материалы и методыunclassified

Evaluation of engraftment and growth dynamics of orthotopic and heterotopic in vivo models of human breast cancer

Lyashenko,

Romanova,

Goncharova

et al. 2024

jour

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Purpose of the study. This work was to assess the engraftment and growth dynamics of breast cancer xenografts during orthotopic and subcutaneous injection using various types of biological material, as well as to develop an adequate model of breast cancer for further research.Materials and methods. We used a disaggregated fragment of a tumor obtained from the patient, a certified breast cancer cell line VT20 – human breast carcinoma; a primary human breast carcinoma cell line. Female immunodeficient mice of the Balb/c Nude line in the amount of 36 animals were used as recipient animals. The subcutaneous and orthotopic models of breast cancer were developed in this project. Tumor growth was observed for 28 days from the moment of injection and tumor nodes were measured 2 times a week until the end of the experiment. Results were assessed using medians and percentiles. The nonparametric Mann-Whitney test was used to assess the significance of differences.Results. The dynamics of the growth of tumor cells when injected into various sites was determined in the process of this work. The most successful in terms of a subcutaneous injection was the injection of tumor cells of the certified VT20 line. By the end of the experiment, the median tumor node of this group was 100.32 mm³. The analysis revealed tumor dynamics with orthotopic injection of tumor material, and the median volume of the tumor node in the group with the passport culture cell VT20 and the primary culture cell reached the same value – 149.22 and 148.25. mm³. It was found that both the cell line and the cell suspension were injected into tumor nodes that reached a significantly larger volume when injected orthotopically.Conclusion. We have obtained a tumor model of breast cancer using various methods of material implantation and with the possibility of further use in testing new pharmacological substances.

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Proactive and reactive roles of TGF-β in cancer

Cited by 13 publications

References 235 publications

Stabilizing vimentin phosphorylation inhibits stem-like cell properties and metastasis of hybrid epithelial/mesenchymal carcinomas

Stabilizing vimentin phosphorylation inhibits stem-like cell properties and metastasis of hybrid epithelial/mesenchymal carcinomas

Mapping Heterogeneity of Hepatocellular Carcinoma by Investigating Hepatocyte-Specific Genes/TFs/Pathways Across Cellular and Tumor Landscapes

Evaluation of engraftment and growth dynamics of orthotopic and heterotopic in vivo models of human breast cancer

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