{"doi":"10.1101/2023.01.03.522657","title":"A multiprotein signaling complex sustains AKT and mTOR/S6K activity necessary for the survival of cancer cells undergoing stress","abstract":"The ability of cancer cells to survive microenvironmental stresses is critical for tumor progression and metastasis; however, how they survive these challenges is not fully understood. Here, we describe a novel multiprotein complex (DockTOR) essential for the survival of cancer cells under stress, triggered by the GTPase Cdc42 and a signaling partner Dock7, which includes AKT, mTOR, and the mTOR regulators TSC1, TSC2, and Rheb. DockTOR enables cancer cells to maintain a low but critical mTORC2-dependent phosphorylation of AKT during serum deprivation by preventing AKT dephosphorylation through an interaction between phospho-AKT and the Dock7 DHR1 domain. This activity stimulates a Raptor-independent but Rapamycin-sensitive mTOR/S6K activity necessary for survival. These findings address long-standing questions of how Cdc42 signals result in mTOR activation and demonstrate how cancer cells survive conditions when growth factor-dependent activation of mTORC1 is off. Determining how cancer cells survive stress conditions could identify vulnerabilities that lead to new therapeutic strategies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395599,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":433813,"name":"Matthew R. Zanotelli","orcid":"0000-0001-8547-6451","position":1,"is_corresponding":false},{"id":937196,"name":"Miao-chong J. Lin","orcid":"0000-0003-3395-070X","position":2,"is_corresponding":false},{"id":562252,"name":"Rebecca Schmitt","orcid":"0000-0002-7845-0808","position":3,"is_corresponding":false},{"id":1171215,"name":"Kai Su Green","orcid":null,"position":4,"is_corresponding":false},{"id":1168189,"name":"Katherine S. Rojas","orcid":null,"position":5,"is_corresponding":false},{"id":1170882,"name":"In Gyu Hwang","orcid":"0000-0002-7461-0333","position":6,"is_corresponding":false},{"id":307283,"name":"Richard A. Cerione","orcid":"0000-0003-4512-5897","position":7,"is_corresponding":false},{"id":309632,"name":"Kristin F. Wilson","orcid":null,"position":8,"is_corresponding":false},{"id":1116252,"name":"Oriana Y. Teran Pumar","orcid":"0000-0002-0536-9056","position":0,"is_corresponding":true}],"reference_count":116,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:19:22.857556Z","pmid":"36711811","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}