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020 ▼a 9781085587730
035 ▼a (MiAaPQ)AAI13428443
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 574
1001 ▼a Bakir, Basil S.
24514 ▼a The Role of p120catenin in the Initiation and Dissemination of Pancreatic Cancer.
260 ▼a [S.l.]: ▼b University of Pennsylvania., ▼c 2019.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2019.
300 ▼a 202 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
500 ▼a Advisor: Rustgi, Anil K.
5021 ▼a Thesis (Ph.D.)--University of Pennsylvania, 2019.
506 ▼a This item must not be sold to any third party vendors.
506 ▼a This item must not be added to any third party search indexes.
520 ▼a Pancreatic cancer is the third leading cause of cancer mortality, the overwhelming majority of which is due to metastasis. The mechanisms of dissemination have been intensively studied, but questions remain as to how epithelial properties are regulated between the primary tumor site and destination as well as to how organotropic patterns of metastasis are determined. We demonstrate, using multiple complementary mouse models, that liver and lung metastatic organotropism in pancreatic cancer is dependent on p120catenin (p120ctn)-mediated epithelial identity. Monoallelic p120ctn loss accelerates KrasG12D-driven PanIN/PDAC formation and metastasis to the liver as well as being sufficient for E-CADHERIN-mediated cell adhesion. In contrast, cells with biallelic p120ctn loss demonstrate marked lung organotropism, although rescue with p120ctn restores liver metastasis. In a p120ctn-independent PDAC model, mosaic E-cadherin knockout shows selective pressure for E-cadherin-positive liver metastasis and E-cadherin-negative lung metastasis. Furthermore, human PDAC and liver metastases support the premise that liver metastases exhibit predominantly epithelial characteristics. RNA-seq demonstrates differential induction of pathways associated with metastasis and epithelial-to-mesenchymal transition in p120ctn-deficient versus p120ctn-wild-type cells. Taken together, p120ctn-mediated epithelial plasticity may be added to the list of emerging concepts underlying metastatic organotropism.
590 ▼a School code: 0175.
650 4 ▼a Cellular biology.
650 4 ▼a Molecular biology.
690 ▼a 0379
690 ▼a 0307
71020 ▼a University of Pennsylvania. ▼b Cell and Molecular Biology.
7730 ▼t Dissertations Abstracts International ▼g 81-02B.
773 ▼t Dissertation Abstract International
790 ▼a 0175
791 ▼a Ph.D.
792 ▼a 2019
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15490458 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK