scholarly journals Upregulation of CD36, a Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis by Increasing MMP28 and Decreasing E-Cadherin Expression

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 252
Author(s):  
James Drury ◽  
Piotr G. Rychahou ◽  
Courtney O. Kelson ◽  
Mariah E. Geisen ◽  
Yuanyuan Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Cancer Metastasis ◽  
Metastatic Potential ◽  
High Expression ◽  
Altered Expression ◽  
Fatty Acid Translocase ◽  
Colorectal Cancer Metastasis ◽  
Effective Therapeutic Strategy ◽  
E Cadherin

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation of MMP28, a novel member of the metallopeptidase family of proteins. Using shRNA-mediated knockdown and overexpression of CD36, we confirmed that CD36 regulates MMP28 expression in CRC cells. siRNA-mediated knockdown of MMP28 decreases invasion of CRC cells, suggesting that MMP28 regulates the metastatic properties of cells downstream of CD36. Importantly, high expression of MMP28 leads to a significant decrease in active E-cadherin and an increase in the products of E-cadherin cleavage, CTF1 and CTF2. In summary, upregulation of CD36 expression promotes the metastatic properties of CRC via upregulation of MMP28 and an increase in E-cadherin cleavage, suggesting that targeting the CD36–MMP28 axis may be an effective therapeutic strategy for CRC metastasis.

scholarly journals Macrophages, as a Promising Strategy to Targeted Treatment for Colorectal Cancer Metastasis in Tumor Immune Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Yingru Zhang ◽  
Yiyang Zhao ◽  
Qi Li ◽  
Yan Wang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Metastatic Potential ◽  
Vital Role ◽  
Phenotypic Switching ◽  
High Plasticity ◽  
Immune Microenvironment ◽  
Promising Strategy ◽  
Tumor Immune Microenvironment ◽  
Colorectal Cancer Metastasis

The tumor immune microenvironment plays a vital role in the metastasis of colorectal cancer. As one of the most important immune cells, macrophages act as phagocytes, patrol the surroundings of tissues, and remove invading pathogens and cell debris to maintain tissue homeostasis. Significantly, macrophages have a characteristic of high plasticity and can be classified into different subtypes according to the different functions, which can undergo reciprocal phenotypic switching induced by different types of molecules and signaling pathways. Macrophages regulate the development and metastatic potential of colorectal cancer by changing the tumor immune microenvironment. In tumor tissues, the tumor-associated macrophages usually play a tumor-promoting role in the tumor immune microenvironment, and they are also associated with poor prognosis. This paper reviews the mechanisms and stimulating factors of macrophages in the process of colorectal cancer metastasis and intends to indicate that targeting macrophages may be a promising strategy in colorectal cancer treatment.

Fusobacterium nucleatum Promotes Colorectal Cancer Metastasis by Modulating KRT7-AS/KRT7

2019 ◽  
Author(s):  
Shujie Chen ◽  
Tingting Su ◽  
Ying Zhang ◽  
Allen Lee ◽  
Jiamin He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Fusobacterium Nucleatum ◽  
Colorectal Cancer Metastasis

scholarly journals IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Chenyang Qiao ◽  
Wenjie Huang ◽  
Jie Chen ◽  
Weibo Feng ◽  
Tongyue Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Cancer Metastasis ◽  
Combined Treatment ◽  
Insulin Like Growth Factor ◽  
Atp Citrate Lyase ◽  
Citrate Lyase ◽  
Elevated Expression ◽  
Igf1r Inhibitor ◽  
Colorectal Cancer Metastasis

AbstractMetastasis is the major reason for the high mortality of colorectal cancer (CRC) patients and its molecular mechanism remains unclear. Here, we report a novel role of Homeobox A13 (HOXA13), a member of the Homeobox (HOX) family, in promoting CRC metastasis. The elevated expression of HOXA13 was positively correlated with distant metastasis, higher AJCC stage, and poor prognosis in two independent CRC cohorts. Overexpression of HOXA13 promoted CRC metastasis whereas downregulation of HOXA13 suppressed CRC metastasis. Mechanistically, HOXA13 facilitated CRC metastasis by transactivating ATP-citrate lyase (ACLY) and insulin-like growth factor 1 receptor (IGF1R). Knockdown of ACLY and IGFIR inhibited HOXA13-medicated CRC metastasis, whereas ectopic overexpression of ACLY and IGFIR rescued the decreased CRC metastasis induced by HOXA13 knockdown. Furthermore, Insulin-like growth factor 1 (IGF1), the ligand of IGF1R, upregulated HOXA13 expression through the PI3K/AKT/HIF1α pathway. Knockdown of HOXA13 decreased IGF1-mediated CRC metastasis. In addition, the combined treatment of ACLY inhibitor ETC-1002 and IGF1R inhibitor Linsitinib dramatically suppressed HOXA13-mediated CRC metastasis. In conclusion, HOXA13 is a prognostic biomarker in CRC patients. Targeting the IGF1-HOXA13-IGF1R positive feedback loop may provide a potential therapeutic strategy for the treatment of HOXA13-driven CRC metastasis.

scholarly journals Targeting the Metabolic Adaptation of Metastatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1641
Author(s):  
Josep Tarragó-Celada ◽  
Marta Cascante
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Breast Cancer Metastasis ◽  
Metabolic Inhibitors ◽  
Current Status ◽  
Metabolic Adaptation ◽  
Metastatic Cells ◽  
Colorectal Cancer Metastasis ◽  
Metastatic Process

Metabolic adaptation is emerging as an important hallmark of cancer and metastasis. In the last decade, increasing evidence has shown the importance of metabolic alterations underlying the metastatic process, especially in breast cancer metastasis but also in colorectal cancer metastasis. Being the main cause of cancer-related deaths, it is of great importance to developing new therapeutic strategies that specifically target metastatic cells. In this regard, targeting metabolic pathways of metastatic cells is one of the more promising windows for new therapies of metastatic colorectal cancer, where still there are no approved inhibitors against metabolic targets. In this study, we review the recent advances in the field of metabolic adaptation of cancer metastasis, focusing our attention on colorectal cancer. In addition, we also review the current status of metabolic inhibitors for cancer treatment.

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