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In this study, we analyzed protein expression, RNA transcription, and signaling pathways to determine the function and mechanism of Yap in breast cancer survival during hypoxic stress. Yap transcription was drastically upregulated by hypoxia in a time-dependent manner. siRNA-mediated Yap knockdown attenuated breast cancer viability and impaired cell proliferation under hypoxic conditions. Yap knockdown induced mitochondrial stress, including mitochondrial membrane potential reduction, mitochondrial oxidative stress, and ATP exhaustion after exposure to hypoxia. It also repressed mitochondrial protective systems, including mitophagy and mitochondrial fusion upon exposure to hypoxia. Finally, our data showed that Yap knockdown suppresses MCF-7 cell migration by inhibiting F-actin transcription and promoting lamellipodium degradation under hypoxic stress. Taken together, Yap maintenance of mitochondrial function and activation of F-actin\/lamellipodium signaling is required for breast cancer survival, migration, and proliferation under hypoxic stress.<\/jats:p>","DOI":"10.1155\/2021\/5212721","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T14:36:02Z","timestamp":1631889362000},"page":"1-10","source":"Crossref","is-referenced-by-count":4,"title":["Yap-Hippo Signaling Activates Mitochondrial Protection and Sustains Breast Cancer Viability under Hypoxic Stress"],"prefix":"10.1155","volume":"2021","author":[{"given":"Chen","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changkuo","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1136-1536","authenticated-orcid":true,"given":"Jian","family":"Tie","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.00199"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.00299"},{"issue":"7","key":"3","doi-asserted-by":"crossref","DOI":"10.1001\/jamaoncol.2020.0249","article-title":"Effect of delayed targeted intraoperative radiotherapy vs whole-breast radiotherapy on local recurrence and survival: long-term results from the TARGIT-a randomized clinical trial in early breast cancer","volume":"6","author":"J. 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