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Consistently, tumor suppressive role of PKC\u03b6 has been established for multiple human cancers. However, recent studies also indicate pro-oncogenic function of PKC\u03b6 without firm understanding of detailed molecular mechanism. Here we report a possible mechanism of oncogenic PKC\u03b6 signaling in the context of breast cancer. We observed that depletion of PKC\u03b6 promotes epithelial morphology in mesenchymal-like MDA-MB-231 cells. The induction of epithelial morphology is associated with significant upregulation of adherens junction (AJ) protein E-cadherin and tight junction (TJ) protein Zonula Occludens-1 (ZO-1). Functionally, depletion of PKC\u03b6 significantly inhibits invasion and metastatic progression. Consistently, we observed higher expression and activation of PKC\u03b6 signaling in invasive and metastatic breast cancers compared to non-invasive diseases. Mechanistically, an oncogenic PKC\u03b6\u2013 NF\u03baB-p65 signaling node might be involved to suppress E-cadherin and ZO-1 expression and ectopic expression of a constitutively active form of NF\u03baB-p65 (S536E-NF\u03baB-p65) significantly rescues invasive potential of PKC\u03b6-depleted breast cancer cells. Thus, our study discovered a PKC\u03b6 - NF\u03baB-p65 signaling pathway might be involved to alter cellular junctional dynamics for breast cancer invasive progression.<\/jats:p>","DOI":"10.1038\/srep12520","type":"journal-article","created":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T12:58:50Z","timestamp":1438088330000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["PKC\u03b6 Promotes Breast Cancer Invasion by Regulating Expression of E-cadherin and Zonula Occludens-1 (ZO-1) via NF\u03baB-p65"],"prefix":"10.1038","volume":"5","author":[{"given":"Arindam","family":"Paul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsha","family":"Danley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswarup","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ossama","family":"Tawfik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumen","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,28]]},"reference":[{"key":"BFsrep12520_CR1","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/nrclinonc.2010.192","volume":"7","author":"L Hutchinson","year":"2010","unstructured":"Hutchinson, L. 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