Mediatory role of BLT2 in the proliferation of KRAS mutant colorectal cancer cells

Park, Jae In; Jang, Jae Hyun; Kim, Jae Hong

doi:10.1016/j.bbamcr.2018.12.006

Cited by 9 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, BLT2 activation by overexpression or by 12-HHT or CAY10583 treatment promoted human bronchial epithelial 16HBE cell proliferation and migration (Liu et al, 2018). Several studies demonstrated that BLT2 is upregulated and participates in pancreatic and colorectal cancer pathogenesis by inducing cancer cell proliferation (Hennig et al, 2008;Park et al, 2019). Here, we detected BLT2 upregulation in the small intestine during the lesion healing process there.…”

Section: Discussionmentioning

confidence: 48%

Leukotriene B₄ Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Matsumoto

Matsuya

Nagai

et al. 2020

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Leukotriene B4 receptor type 2 (BLT2) is a low-affinity leukotriene B4 (LTB4) receptor that is highly expressed in intestinal epithelial cells. Previous studies demonstrated the protective role of BLT2 in experimentally-induced colitis. However, its role in intestinal lesion repair is not fully understood. We investigated the role of BLT2 in the healing of indomethacin-induced intestinal lesions in mice. There was no significant different between WT and BLT2KO mice in terms of the development of indomethacininduced intestinal lesions. However, healing of these lesions was significantly impaired in BLT2-deficient (BLT2KO) mice compared with wild type (WT) mice. In contrast, transgenic mice with intestinal epithelium-specific BLT2 overexpression presented with superior ileal lesion healing relative to WT mice. An immunohistochemical study showed that the number of Ki-67-proliferative cells was markedly increased during the healing of intestinal lesions in WT mice but significantly attenuated in BLT2KO mice.Exposure of cultured mouse intestinal epithelial cells to CAY10583, a BLT2 agonist, promoted wound healing and cell proliferation in a concentration-dependent manner.Nevertheless, these responses were abolished under serum-free conditions. The CAY10583-induced proliferative effect was also negated by Go6983, a protein kinase C (PKC) inhibitor, U-73122, a phospholipase C (PLC) inhibitor, LY255283, a BLT2 antagonist, and pertussis toxin (PTX) that inhibits GPCR signaling via Gi/o proteins. Thus, BLT2 plays an important role in intestinal wound repair. Moreover, this effect is mediated by the promotion of epithelial cell proliferation via the Gi/o-proteindependent-and PLC/PKC signaling pathways. The BLT2 agonists are potential therapeutic agents for the treatment of intestinal lesions.

show abstract

Section: Discussionmentioning

confidence: 48%

Leukotriene B₄ Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Matsumoto

Matsuya

Nagai

et al. 2020

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Its expression has been associated with invasion and metastasis of lung cancer and breast cancer [15] [16]. It was also confirmed that high expression of LTB4R2 promoted CRC cell proliferation [17]. The Alpha-B crystallin (CRYAB), a member of the small molecular heat shock protein family, was first identified as a major structural protein in the lens of the eye.…”

Section: Discussionmentioning

confidence: 85%

Screening of Colon Cancer Apoptosis-Related Genes Based on Bioinformatics and Construction of Survival Prognostic Model

Zhao¹,

Wu²,

Xu³

et al. 2023

JBM

View full text Add to dashboard Cite

This study aimed to explore the prognostic value of Anoikis-related genes (ANRGs) in colon cancer using bioinformatics and construct a prognostic model based on ANRGs. ANRGs integrated from GeneCard and Harmonizome were used to identify CRC subtypes and construct a prognostic model for CRC patients. The immune microenvironment (TME) between different subtypes was also investigated. Finally, a line chart based on ANRGs was provided for clinical use, and decision curve analysis (DCA) was performed to determine the potential benefits of the model for clinical strategies. We identified 14 differential expression genes (DEGs) related to survival in CRC Anoikis, and selected 7 genes to construct the prognostic model. The prognostic risk score was determined as independent prognostic factor. Functional analysis showed that high-risk and low-risk groups had different immune infiltration status. Combined with CRC clinical pathological characteristics, a line chart was constructed, and DCA analysis showed that this model could benefit from clinical treatment strategies. This study explored 7 prognostic-associated risk genes related to CRC and constructed a line chart, which can provide important reference value for clinical doctors to choose personalized treatment for CRC patients.

show abstract

“…LTB4R2 encodes the leukotriene B4 receptor 2, a G-protein-coupled receptor regulating chemotaxis and wound healing. In addition to inflammatory processes, this receptor has been shown to be implicated in invasion and metastatic colonization of lung and other cancers [ 36 , 37 , 38 ]. In this work, we found LTB4R2 to be a druggable essentiality gene in SCC, whereas in a previous work we found LTB4R2 to be a vulnerability specifically associated with the presence of KRAS mutation in lung AD [ 9 ]; thus, the sensitivity to the KO of this gene may be context-specific and not limited to a single lung cancer subtype.…”

Section: Discussionmentioning

confidence: 99%

CSNK1A1, KDM2A, and LTB4R2 Are New Druggable Vulnerabilities in Lung Cancer

Sauta

Reggiani

Torricelli

et al. 2021

Cancers

View full text Add to dashboard Cite

Lung cancer is the leading cause of cancer-related human death. It is a heterogeneous disease, classified in two main histotypes, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), which is further subdivided into squamous-cell carcinoma (SCC) and adenocarcinoma (AD) subtypes. Despite the introduction of innovative therapeutics, mainly designed to specifically treat AD patients, the prognosis of lung cancer remains poor. In particular, available treatments for SCLC and SCC patients are currently limited to platinum-based chemotherapy and immune checkpoint inhibitors. In this work, we used an integrative approach to identify novel vulnerabilities in lung cancer. First, we compared the data from a CRISPR/Cas9 dependency screening performed in our laboratory with Cancer Dependency Map Project data, essentiality comprising information on 73 lung cancer cell lines. Next, to identify relevant therapeutic targets, we integrated dependency data with pharmacological data and TCGA gene expression information. Through this analysis, we identified CSNK1A1, KDM2A, and LTB4R2 as relevant druggable essentiality genes in lung cancer. We validated the antiproliferative effect of genetic or pharmacological inhibition of these genes in two lung cancer cell lines. Overall, our results identified new vulnerabilities associated with different lung cancer histotypes, laying the basis for the development of new therapeutic strategies.

show abstract

Mediatory role of BLT2 in the proliferation of KRAS mutant colorectal cancer cells

Cited by 9 publications

References 32 publications

Leukotriene B₄ Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Leukotriene B₄ Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Screening of Colon Cancer Apoptosis-Related Genes Based on Bioinformatics and Construction of Survival Prognostic Model

CSNK1A1, KDM2A, and LTB4R2 Are New Druggable Vulnerabilities in Lung Cancer

Contact Info

Product

Resources

About

Mediatory role of BLT2 in the proliferation of KRAS mutant colorectal cancer cells

Cited by 9 publications

References 32 publications

Leukotriene B4 Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Leukotriene B4 Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Screening of Colon Cancer Apoptosis-Related Genes Based on Bioinformatics and Construction of Survival Prognostic Model

CSNK1A1, KDM2A, and LTB4R2 Are New Druggable Vulnerabilities in Lung Cancer

Contact Info

Product

Resources

About

Leukotriene B₄ Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation

Leukotriene B₄ Receptor Type 2 Accelerates the Healing of Intestinal Lesions by Promoting Epithelial Cell Proliferation