title: p120-catenin modulates airway epithelial cell migration induced by cigarette smoke.
abstract: Cigarette smoking has been linked to almost all major types of cancer. Emerging evidence suggests that smoking initiates transformed cell growth and migration by disrupting cell-cell interactions in the polarized mucosal epithelium. Together with other adherens junction proteins, p120-catenin (p120ctn) maintains cell-cell adhesion through its direct interaction with E-cadherin (E-cad). Mislocalization and/or loss of p120ctn have been reported in all lung cancer subtypes and are related to poor prognosis. Here, we showed that p120ctn modulates smoke-induced cell migration via the EGFR/Src-P pathway. Chemical blockade of EGFR/Src signaling inhibited smoke-induced activation of cofilin (an actin severing protein) and promoted cell migration in the presence of p120ctn but had little effect on blocking migration in the absence of p120ctn. These data suggested that smoke-induced cell migration was mediated via an EGFR/Src-dependent signaling pathway in cells that expressed p120ctn, but upon loss of p120ctn, migration continued to occur via an alternative, EGFR/Src-independent pathway. Thus, gradual loss of membrane p120ctn with lung cancer progression may contribute to reduced effectiveness of conventional chemotherapies, such as those directed against EGFR.
authors: Francis I. Proctor Foundation, University of California, San Francisco, CA 94143-0412, USA.
authors: Lili
authors: L
authors: Zhang
authors: Marianne
authors: M
authors: Gallup
authors: Lorna
authors: L
authors: Zlock
authors: Walter
authors: W
authors: Finkbeiner
authors: Nancy A
authors: NA
authors: McNamara
mesh_terms: D022005:Adherens Junctions / Q000235:genetics; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066246:ErbB Receptors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*; D020032:Tyrphostins / Q000494:pharmacology; D019061:src-Family Kinases / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012906:Smoke; D020032:Tyrphostins; C101044:RTKI cpd; C512478:EGFR protein, human; D066246:ErbB Receptors; D019061:src-Family Kinases; D000095002:Delta Catenin