{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:04:16Z","timestamp":1789391056990,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yangpu Hospital Affiliated to Tongji University","award":["yzxxk202605"],"award-info":[{"award-number":["yzxxk202605"]}]},{"name":"Tongji University Affiliated Yangpu Hospital","award":["Ye2202105"],"award-info":[{"award-number":["Ye2202105"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>LIM and calponin homology domain-containing protein 1 (LIMCH1) has recently gained attention as a functionally perplexing factor in human cancers, with studies attributing both tumor-suppressive and tumor-promoting properties that defy simple categorization. Originally described as an actin-associated cytoskeletal protein that promotes non-muscle myosin-IIA (NM-IIA) activity and thereby curtails cell migration, LIMCH1 has more recently been linked to diverse oncogenic pathways across a range of tumor types. In lung adenocarcinoma and clear-cell renal cell carcinoma, diminished LIMCH1 expression is associated with more aggressive clinical behavior and reduced overall survival, aligning with a tumor-suppressive role. By comparison, in triple-negative and invasive breast cancers and in cervical squamous cell carcinoma, increased LIMCH1 expression correlates with enhanced metastatic spread, immune escape, and unfavorable outcomes, suggesting a pro-oncogenic function. In this review, findings from over 30 published studies are integrated with an original TCGA pan-cancer expression and survival analysis to propose that LIMCH1 is best understood as a context-dependent conditional regulator rather than as a classical tumor suppressor or oncogene. Based on the available evidence, we propose a hypothesis-generating conceptual framework in which its ultimate phenotypic effect is shaped by three interacting contextual determinants: (i) TP53 mutation status (determining whether the HUWE1-p53 axis is intact); (ii) tumor matrix stiffness (modulating actomyosin contractility and migration mode); and (iii) upstream signaling cues (e.g., MAPK\/ERK, TGF\u03b2). Of note, other tumor-lineage and microenvironmental factors may also contribute and warrant further investigation. This framework resolves the apparent functional duality of LIMCH1 in a cancer type-specific manner and provides critical guidance for future mechanistic research, standardized detection workflows, and the clinical translation of LIMCH1-based biomarkers.<\/jats:p>","DOI":"10.3390\/ijms27188144","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"8144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LIMCH1 in Cancer: A Context-Dependent Modulator Beyond the Tumor Suppressor\u2013Oncogene Dichotomy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2302-9930","authenticated-orcid":false,"given":"Mengying","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9292-2675","authenticated-orcid":false,"given":"Hua","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200090, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1091\/mbc.e15-04-0218","article-title":"LIMCH1 regulates nonmuscle myosin-II activity and suppresses cell migration","volume":"28","author":"Lin","year":"2017","journal-title":"Mol. 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