{"doi":"10.1016/j.celrep.2021.109162","title":"Non-autonomous regulation of germline stem cell proliferation by somatic MPK-1/MAPK activity in C. elegans","abstract":"Extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) is a major positive regulator of cell proliferation, which is often upregulated in cancer. However, few studies have addressed ERK/MAPK regulation of proliferation within a complete organism. The Caenorhabditis elegans ERK/MAPK ortholog MPK-1 is best known for its control of somatic organogenesis and germline differentiation, but it also stimulates germline stem cell proliferation. Here, we show that the germline-specific MPK-1B isoform promotes germline differentiation but has no apparent role in germline stem cell proliferation. By contrast, the soma-specific MPK-1A isoform promotes germline stem cell proliferation non-autonomously. Indeed, MPK-1A functions in the intestine or somatic gonad to promote germline proliferation independent of its other known roles. We propose that a non-autonomous role of ERK/MAPK in stem cell proliferation may be conserved across species and various tissue types, with major clinical implications for cancer and other diseases.","journal":"Cell Reports","year":2021,"id":167910,"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":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"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":576551,"name":"Benjamin Dufour","orcid":null,"position":1,"is_corresponding":false},{"id":575806,"name":"Pier-Olivier Martel","orcid":"0009-0008-1356-7387","position":2,"is_corresponding":false},{"id":576552,"name":"Xavier Lechasseur","orcid":null,"position":3,"is_corresponding":false},{"id":576553,"name":"Amani Ange Danielle Brou","orcid":null,"position":4,"is_corresponding":false},{"id":575807,"name":"Vincent Roy","orcid":"0000-0002-3506-4384","position":5,"is_corresponding":false},{"id":575808,"name":"Yunqing Chen","orcid":"0000-0002-6424-2952","position":6,"is_corresponding":false},{"id":438022,"name":"Judith Kimble","orcid":"0000-0001-5622-2073","position":7,"is_corresponding":false},{"id":575809,"name":"Patrick Narbonne","orcid":"0000-0002-2752-4205","position":8,"is_corresponding":false},{"id":575805,"name":"Sarah L. Robinson","orcid":"0000-0002-4906-7658","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:46:02.603031Z","pmid":"34038716","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":[]}