Sürdürülebilir Kalkınma Amaçları

• 2

• MakaleAçık Erişim2026Scopus SJRQ2/r/kostu/10651
  CRISPR screens reveal YAP/TEAD axis as a mediator of drug-tolerant cells in EGFR-mutant NSCLC

  Yusuf, Muhammed

  Despite initial responses, most patients with metastatic lung cancer—including those with EGFR mutations—ultimately develop resistance to targeted therapies. To systematically uncover mechanisms underlying this resistance, genome-wide CRISPR knockout and activation screens were conducted in EGFR-mutant lung cancer cell lines treated with EGFR inhibitors such as osimertinib and gefitinib. These screens highlighted a recurrent involvement of genes associated with the Hippo signaling pathway. Notably, a subset of tumor cells, termed 'persister' cells, survive initial osimertinib exposure by engaging non-genetic, transcriptional adaptation mechanisms that promote drug tolerance. Our studies, integrating both genetic and pharmacological approaches, identified Hippo pathway activation as a key driver of this drug-tolerant state. Importantly, co-inhibition of EGFR and the Hippo signaling axis led to a pronounced reduction in cell viability in both established cell lines and patient-derived organoids. These findings propose that dual targeting of EGFR and Hippo signaling may offer a promising therapeutic approach to overcome resistance in EGFR-mutant lung cancer.

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  AtıfScopus3·WoS3·OpenAlex2

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• MakaleAçık Erişim2026Scopus SJRQ1/r/kostu/10545
  Wound healing activity of Sweetgum oil (Liquidambar orientalis L. balsam): characterization of its mechanism of action on HaCaT human keratinocyte cells and possible responsible active constituents

  Yusuf, Muhammed; Gökşen-Ekiz, Burcu; Engür-Öztürk, Selin; Dikmen, Miriş; Levent, Serkan; Öztürk, Yusuf

  Background: Sweetgum oil (Liquidambar orientalis Mill.; Styrax liquidus) is traditionally used in Turkey for wounds and burns, yet its cellular mechanisms remain unclear. Methods: Two locally sourced sweetgum oil samples were tested in human HaCaT keratinocytes. Cytotoxicity was assessed by MTT. Proliferation and migration were quantified using RTCA-DP and scratch assays. COL1A1 mRNA was measured by TaqMan RT-PCR. Phytochemical profiling employed IT-TOF/MS; titrated Centella asiatica extract (TECA) was the positive control. Results: Non-toxic concentrations were identified at 0.001–0.1 μg/mL. At 0.001 μg/mL, sweetgum oil significantly increased keratinocyte proliferation and migration in a time-dependent manner (RTCA-DP; p < 0.05 to p < 0.01), accelerating scratch-wound closure versus control. COL1A1 expression was unchanged. IT-TOF/MS indicated phenylpropyl cinnamate as the dominant constituent in both samples. Conclusions: Sweetgum oil promotes re-epithelialization-related processes primarily by enhancing keratinocyte proliferation and migration rather than collagen induction. These findings support sweetgum oil as a promising natural wound-healing agent and motivate in vivo validation.

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  AtıfScopus1·WoS1

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