Lysophosphatidic acid-induced amphiregulin secretion by cancer-associated fibroblasts augments cancer cell invasion

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dc.contributor.authorB Y Jeong-
dc.contributor.authorK H Cho-
dc.contributor.authorK J Jeong-
dc.contributor.authorS J Cho-
dc.contributor.authorMinho Won-
dc.contributor.authorS H Kim-
dc.contributor.authorN H Cho-
dc.contributor.authorG M Hur-
dc.contributor.authorS H Yoon-
dc.contributor.authorH W Park-
dc.contributor.authorG B Mills-
dc.contributor.authorH Y Lee-
dc.date.accessioned2022-10-13T16:32:23Z-
dc.date.available2022-10-13T16:32:23Z-
dc.date.issued2022-
dc.identifier.issn0304-3835-
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/30444-
dc.description.abstractCancer-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.-
dc.publisherElsevier-
dc.titleLysophosphatidic acid-induced amphiregulin secretion by cancer-associated fibroblasts augments cancer cell invasion-
dc.title.alternativeLysophosphatidic acid-induced amphiregulin secretion by cancer-associated fibroblasts augments cancer cell invasion-
dc.typeArticle-
dc.citation.titleCancer Letters-
dc.citation.number0-
dc.citation.endPage215946-
dc.citation.startPage215946-
dc.citation.volume551-
dc.contributor.affiliatedAuthorMinho Won-
dc.contributor.alternativeName정보영-
dc.contributor.alternativeName조경화-
dc.contributor.alternativeName정강진-
dc.contributor.alternativeName조수진-
dc.contributor.alternativeName원민호-
dc.contributor.alternativeName김승화-
dc.contributor.alternativeName조남훈-
dc.contributor.alternativeName허강민-
dc.contributor.alternativeName윤세희-
dc.contributor.alternativeName박환우-
dc.contributor.alternativeNameMills-
dc.contributor.alternativeName이회영-
dc.identifier.bibliographicCitationCancer Letters, vol. 551, pp. 215946-215946-
dc.identifier.doi10.1016/j.canlet.2022.215946-
dc.subject.keywordAmphiregulin-
dc.subject.keywordCancer-associated fibroblasts-
dc.subject.keywordLysophosphatidic acid-
dc.subject.keywordYes-associated protein-
dc.subject.keywordCancer invasion-
dc.subject.localAmphiregulin-
dc.subject.localYes-associated protein-
dc.subject.localCancer invasion-
dc.subject.localcancer invasion-
dc.description.journalClassY-
Appears in Collections:
Division of Bio Technology Innovation > BioProcess Engineering Center > 1. Journal Articles
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