Lysophosphatidic acid-induced amphiregulin secretion by cancer-associated fibroblasts augments cancer cell invasion.
-
Authors
-
-
Jeong, Bo Young1
-
Cho, Kyung Hwa2
-
Jeong, Kang Jin3
-
Cho, Su Jin2
-
Won, Minho4
-
Kim, Seung Hwa2
-
Cho, Nam Hoon5
-
Hur, Gang Min6
-
Yoon, Se-Hee7
-
Park, Hwan-Woo8
-
Mills, Gordon B3
-
Lee, Hoi Young9
-
1
Department of Pharmacology, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea; Division of Oncological Sciences Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA.
,
(North Korea)
-
2
Department of Pharmacology, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea.
,
(North Korea)
-
3
Division of Oncological Sciences Knight Cancer Institute, Oregon Health and Science University, Portland, OR, 97201, USA.
-
4
Biotechnology Process Engineering Center, Korea Research Institute of Bioscience & Biotechnology, Cheongju, 28116, Republic of Korea; Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.
,
(North Korea)
-
5
Department of Pathology, College of Medicine, Yonsei University, Seoul, 03722, Republic of Korea.
,
(North Korea)
-
6
Department of Pharmacology, College of Medicine, Chungnam National University, Daejeon, 35015, Republic of Korea.
,
(North Korea)
-
7
Division of Nephrology and Department of Internal Medicine, College of Medicine, Konyang University, Daejeon, 35364, Republic of Korea.
,
(North Korea)
-
8
Department of Cell Biology, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea.
,
(North Korea)
-
9
Department of Pharmacology, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea. Electronic address: [email protected].
,
(North Korea)
- Type
- Published Article
- Journal
-
Cancer letters
- Publication Date
-
Dec 28, 2022
- Volume
-
551
- Pages
-
215946–215946
- Identifiers
-
DOI: 10.1016/j.canlet.2022.215946
-
PMID: 36209972
- Source
-
Medline
- Keywords
-
- Language
-
English
- License
-
Unknown
Abstract
Cancer-associated fibroblasts (CAFs) are key structural components of the tumor microenvironment and are closely associated with tumor invasion and metastasis. Lysophosphatidic acid (LPA) is a biolipid produced extracellularly and involved in tumorigenesis and metastasis. LPA has recently been implicated in the education and transdifferentiation of normal fibroblasts (NFs) into CAFs. However, little is known about the effects of LPA on CAFs and their participation in cancer cell invasion. In the present study, we identified a critical role of LPA-induced amphiregulin (AREG) secreted from CAFs in cancer invasiveness. CAFs secrete higher amounts of AREG than NFs, and LPA induces AREG expression in CAFs to augment their invasiveness. Strikingly, knocking out the AREG gene in CAFs attenuates cancer invasiveness and metastasis. Mechanistically, LPA induces Yes-associated protein (YAP) activation and Zinc finger E-box binding homeobox 1 (Zeb1) expression through the LPAR1 and LPAR3/Gi/Rho signaling axes, leading to AREG expression. Furthermore, we provide evidence that metformin, a biguanide derivative, significantly inhibits LPA-induced AREG expression in CAFs to attenuate cancer cell invasiveness. Collectively, the present data show that LPA induces AREG expression through YAP and Zeb1 in CAFs to promote cancer cell invasiveness, with the process being inhibited by metformin, providing potential biomarkers and therapeutic avenues to interdict cancer cell invasion. Copyright © 2022. Published by Elsevier B.V.
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This record was last updated on 10/18/2023 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at
https://www.ncbi.nlm.nih.gov/pubmed/36209972
