Hypoxia-induced autophagy contributes to the invasion of salivary adenoid cystic carcinoma through the HIF-1α/BNIP3 signaling pathway.
Adenoid cystic carcinoma (ACC) is one of the most common types of salivary gland malignancy in the head and neck, and its aggressive ability to invade and metastasize is an important reason for its poor survival rates. Our previous investigations confirmed that autophagy‑associated gene expression is closely associated with the occurrence and development of ACC. On this basis, the present study further investigated hypoxia‑induced autophagy and its role in tumor invasion. Cobalt chloride (CoCl2) was used to mimic hypoxia. The results of the present study indicated that autophagosome formation and upregulation of autophagy‑associated microtubule‑associated protein 1 light chain 3 and Beclin 1 were observed in ACC‑M cells in response to CoCl2. The hypoxia‑inducible factor 1α/B cell lymphoma 2/adenovirus E1B 19K‑interacting protein 3 signaling pathway was involved in hypoxia‑induced autophagy in ACC. Furthermore, inhibition of autophagy by chloroquine markedly attenuated the tumor invasion induced by mimetic hypoxia in ACC. These results suggested that hypoxia‑induced autophagy may serve as a potential target for the future treatment of ACC.
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Haiwei
H
Wu
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Shengyun
S
Huang
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Zhanwei
Z
Chen
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Wenlei
W
Liu
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Xiaoqing
X
Zhou
Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Dongsheng
D
Zhang
D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D000071186:Beclin-1; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D003035:Cobalt / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; C090121:BNIP3 protein, human; D000071186:Beclin-1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C502070:MAP1LC3B protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D003035:Cobalt; D002738:Chloroquine; C018021:cobaltous chloride