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CSCC possesses significant heterogeneity and the treatment presents a formidable challenge. To gain a clear insight into the diverse nature of these tumors, the development of an in vitro cell line model is essential. However, there are few cell lines that were established, and only one skin SCC cell line is available on the ATCC. In the present study, we established and characterized a novel ACSCC1 cell line from the advanced-stage treatment na\u00efve cutaneous SCC originating from the forearm of the Indian patient. The keratin expression profile showed the epithelial origin of the cell line, ploidy and karyotyping revealed the hyperdiploid population; ACSCC1 showed an increased tumorigenic and metastatic potential. Further, our cell line showed higher invasive, migratory potential and epithelial-mesenchymal-transition (EMT). Additionally, the Transmission electron microscopy (TEM) results showed an\u00a0aberrant mitochondrial morphology and reduction in the cellular junctions. Further, our whole genome sequencing (WGS) analysis showed mutations in the cancer-related genes. Overall, the novel ACSCC1 cell line can be used to decipher the molecular signaling in the cancer stem cells (CSCs); targeting the CSCs population may help in understanding the tumor recurrence.<\/jats:p>","DOI":"10.1007\/s13577-025-01237-4","type":"journal-article","created":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T06:50:48Z","timestamp":1748155848000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Establishment and molecular characterization of the novel cutaneous squamous cell carcinoma cell line from advanced-stage Indian patient"],"prefix":"10.1007","volume":"38","author":[{"given":"Darshan","family":"Mehta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Paradkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Nayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharat","family":"Rekhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhabani","family":"Mohanty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"Chaudhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3693-5620","authenticated-orcid":false,"given":"Sanjeev K","family":"Waghmare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,25]]},"reference":[{"key":"1237_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94435-7","author":"MCG Winge","year":"2023","unstructured":"Winge MCG, Kellman LN, Guo K, Tang JY, Swetter SM, Aasi SZ, et al. 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The authors have no relevant financial or non-financial interests to disclose. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The cell line ACSCC1 was established from the cutaneous SCC cancer patient samples from Tata Memorial Hospital (Mumbai, India). This study was performed in line with the principles of Helsinki. Approval was granted by the Institutional Human Ethics Committee, ACTREC (Dated June 21st 2023\u2013 IEC #900939). The Institutional Animal Ethics Committee (IAEC), ACTREC has approved all the animal experiments. We have adhered to the CPSEA criteria set by the Indian Ministry of Environment and Forests for conducting all animal research. In addition, we adhered to the Arrive criteria and the requirements for care and animal welfare set by the National Research Council in Washington, DC. (July 2023- IAEC 20\/2023).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human and animal rights"}},{"value":"Informed consent was obtained from all the individual participants included in the study. The Institutional Human Ethics Committee, ACTREC has approved this study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for the publication of the images in this manuscript.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}],"article-number":"108"}}