{"doi":"10.1101/2021.04.27.441690","title":"Liver Endothelium Promotes HER3-mediated Cell Survival in <i>KRAS</i> Wild-type and Mutant Colorectal Cancer Cells","abstract":"ABSTRACT We previously showed that liver endothelial cells (ECs) secreted soluble factors in a paracrine fashion and activated human epidermal growth factor receptor 3 (HER3, also known as ERBB3) for promoting colorectal cancer (CRC) growth and chemoresistance. However, RAS proteins play a critical role in receptor tyrosine kinase signaling pathways, and KRAS mutations mediate CRC resistance to therapies targeting EGFR, another HER protein. Therefore, the role of KRAS mutation status in EC-induced HER3 activation and CRC survival was investigated as it has therapeutic implications. We used CRC cell lines and patient-derived xenografts harboring KRAS wild-type or mutant genes and demonstrated that liver EC-secreted factors promoted HER3-mediated CRC cell growth independent of KRAS mutation status. Also, blocking HER3 in CRC cells by siRNAs or a HER3 antibody seribantumab blocked EC-induced CRC survival. Our findings highlight the potential of utilizing HER3 targeted therapies for treating patients with mCRC independent of RAS mutational status.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":224130,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9471,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":571523,"name":"Michelle L. Wright","orcid":"0000-0002-9348-8740","position":1,"is_corresponding":false},{"id":825879,"name":"Rajat Bhattacharya","orcid":"0000-0001-5693-6754","position":2,"is_corresponding":false},{"id":304960,"name":"Fan Fan","orcid":"0000-0003-1463-3610","position":3,"is_corresponding":false},{"id":585708,"name":"Ali Vaziri‐Gohar","orcid":"0000-0002-6924-8691","position":4,"is_corresponding":false},{"id":262927,"name":"Jordan M. Winter","orcid":"0000-0002-5200-6557","position":5,"is_corresponding":false},{"id":262246,"name":"Zhenghe Wang","orcid":"0000-0003-1546-1080","position":6,"is_corresponding":false},{"id":2243,"name":"Sanford D. Markowitz","orcid":"0000-0001-5369-5254","position":7,"is_corresponding":false},{"id":2244,"name":"Joseph Willis","orcid":"0000-0003-1782-886X","position":8,"is_corresponding":false},{"id":3650,"name":"Lee M. Ellis","orcid":"0000-0001-8082-4904","position":9,"is_corresponding":false},{"id":585715,"name":"Rui Wang","orcid":"0000-0001-5794-7201","position":10,"is_corresponding":false},{"id":825878,"name":"Moeez Rathore","orcid":"0000-0002-0999-0747","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:54:14.760456Z","pmid":null,"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":[]}