scholarly journals The Colorectal Cancer Microenvironment: Strategies for Studying the Role of Cancer-Associated Fibroblasts

2018 ◽  
pp. 87-98 ◽  
Author(s):  
Rahul Bhome ◽  
Massimiliano Mellone ◽  
Katherine Emo ◽  
Gareth J. Thomas ◽  
A. Emre Sayan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Microenvironment ◽  
Cancer Associated Fibroblasts

scholarly journals The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment

2020 ◽  
Vol 9 (1) ◽  
pp. 8-19
Author(s):  
Juha P. Väyrynen ◽  
Koichiro Haruki ◽  
Mai Chan Lau ◽  
Sara A. Väyrynen ◽  
Rong Zhong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Macrophage Polarization ◽  
Cancer Microenvironment ◽  
Prognostic Role

scholarly journals The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2296
Author(s):  
Maurice Michel ◽  
Leonard Kaps ◽  
Annett Maderer ◽  
Peter R. Galle ◽  
Markus Moehler
Keyword(s):  
Colorectal Cancer ◽  
Stromal Cells ◽  
Tp53 Gene ◽  
Cancer Associated Fibroblasts ◽  
P53 Mutations ◽  
The One ◽  
Immunosuppressive Cells ◽  
And Personalized Medicine ◽  
Therapy Treatment

Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.

Cancer-Secreted Exosomal HSPC111 Promotes Colorectal Cancer Liver Metastasis By Reprogramming Lipid Metabolism in Cancer-Associated Fibroblasts

2021 ◽  
Author(s):  
Chong Zhang ◽  
Xiang-Yu Wang ◽  
Peng Zhang ◽  
Tao-Chen He ◽  
Jia-Hao Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Liver Metastasis ◽  
Metabolic Reprogramming ◽  
Regulation Mechanism ◽  
Dependent Manner ◽  
Cancer Associated Fibroblasts ◽  
Metastatic Niche

Abstract Background: Metastasis and metabolic deregulation are two of the major hallmarks of cancer. Recent studies have revealed the critical driving role of metabolic reprogramming of tumor cells to promote colorectal cancer (CRC) metastasis. However, little is known about the metabolic alterations of cancer-associated fibroblasts (CAFs) in the pre-metastatic niche and how these changes facilitate CRC metastasis.Methods: Liquid chromatography-mass spectrometry (LC-MS) and Isobaric Tags for Relative and Absolute Quantitation (i-TRAQ) method were performed to identify the comparative metabolites and proteins expression in CAFs treated with exosomes derived from CRC cells, respectively. Tissue Microarray (TMA) was used to evaluate the level of HSPC111 in patient’s primary CRC tissues with or without liver metastasis. Co-immunoprecipitation (Co-IP), RNA-seq, chromatin immunoprecipitation (ChIP) migration and wound healing assay and immunofluorescence staining were employed to explore the expression regulation mechanism of exosomal HSPC111 in CAFs. Xenograft models were used to determine whether exosomal HSPC111 can remolding pre-metastatic niche of CAFs to promote CRC liver metastasis (CRLM) in vivo.Results: Here, we demonstrate that CRC cell-secreted exosomal HSPC111 induces a lipid metabolism reprogramming process in CAFs. Importantly, our results indicate that CRC patients with liver metastasis had significantly high level of HSPC111 in CRC tissues than CRC patients without liver metastasis. Mechanistically, HSPC111 upregulate the level of acetyl-CoA and histone acetylation by phosphorylating of ATP-citrate lyase (ACLY) in CAFs. This lipid metabolism reprogramming in CAFs facilitates CXCL5 secretion in vitro and pre-metastatic niche formation in the liver to promote CRLM in an exosomal HSPC111-dependent manner in vivo. In addition, conditioned medium (CM) from CAFs induce EMT of CRC cells by down-regulating E-cadherin levels and up-regulating Vimentin and Snail levels, which could be abolished by CXCL5-neutralizing antibody and CXCR2 inhibitor navarixin. Moreover, the HSPC111-ACLY association in CAFs was reinforced by CXCL5-CXCR2 axis, further promoting exosomal HSPC111 secretion from CRC cells to form a feedforward regulatory loop.Conclusion: Our present study reveals a novel insight into the pro-metastatic role of lipid metabolism reprogramming in CAFs and suggests the CXCL5-CXCR2 axis may be a promising target for halting CRLM.

The Contemporary Role of Resection and Ablation in Colorectal Cancer Liver Metastases

2020 ◽  
Vol 04 (03) ◽  
pp. 291-302
Author(s):  
Mariam F. Eskander ◽  
Christopher T. Aquina ◽  
Aslam Ejaz ◽  
Timothy M. Pawlik
Keyword(s):  
Colorectal Cancer ◽  
Portal Vein ◽  
Surgical Oncology ◽  
Portal Vein Ligation ◽  
Safe Alternative ◽  
Colorectal Cancer Liver Metastases ◽  
Liver Remnant ◽  
New Era ◽  
Ablation Therapy

AbstractAdvances in the field of surgical oncology have turned metastatic colorectal cancer of the liver from a lethal disease to a chronic disease and have ushered in a new era of multimodal therapy for this challenging illness. A better understanding of tumor behavior and more effective systemic therapy have led to the increased use of neoadjuvant therapy. Surgical resection remains the gold standard for treatment but without the size, distribution, and margin restrictions of the past. Lesions are considered resectable if they can safely be removed with tumor-free margins and a sufficient liver remnant. Minimally invasive liver resections are a safe alternative to open surgery and may offer some advantages. Techniques such as portal vein embolization, association of liver partition with portal vein ligation for staged hepatectomy, and radioembolization can be used to grow the liver remnant and allow for resection. If resection is not possible, nonresectional ablation therapy, including radiofrequency and microwave ablation, can be performed alone or in conjunction with resection. This article presents the most up-to-date literature on resection and ablation, with a discussion of current controversies and future directions.

The Critical Role of the miR-21-MEG2 Axis in Colorectal Cancer

2020 ◽  
Vol 30 (6) ◽  
pp. 509-518
Author(s):  
Zengtao Bao ◽  
Shanting Gao ◽  
Baoming Zhang ◽  
Wenchao Shi ◽  
Aimin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Critical Role

THE ROLE OF RADIATION METHODS IN DIAGNOSIS AND STAGING OF COLORECTAL CANCER

2018 ◽  
pp. 93-102
Author(s):  
V. A. Solodkiy ◽  
N. V. Nudnov ◽  
V. D. Chhikvadze ◽  
U. S. Stanojevich ◽  
N. I. Sergeev ◽  
...  
Keyword(s):  
Colorectal Cancer

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document