Enhancer Addiction in Lung Squamous Cell Carcinoma Uncovered, Pinning PTPRZ1-MDK as a Novel Targetab

A study led by researchers from City University of Hong Kong, Chinese Academy of Medical Sciences and Peking Union Medical College, The First Affiliated Hospital of Xi’an Jiaotong University, and Northwest University, published in Advanced Science, provides new direction for Lung Squamous Cell Carcinoma (LUSC), which currently lacks effective targeted therapies. The research reveals that “enhancer addiction” --the reprogramming of genomic enhancer regions --is a hallmark of LUSC, driving tumorigenesis through a network of key transcription factors (SOX2, TP63, KLF5, GRHL2). Multi-omics integration identified the receptor tyrosine phosphatase PTPRZ1 as a top enhancer --driven oncogene. Functional validation demonstrated that PTPRZ1 is essential for tumor cell proliferation, migration, and in vivo tumor growth. Spatial transcriptomics further pinpointed Midkine (MDK) as its activating ligand in the tumor microenvironment, forming an oncogenic PTPRZ1-MDK axis that promotes PI3K signaling.

Figure 3. Regulation of PTPRZ1 by SOEs in LUSC

HySigen’s PTPRZ1-KOCell Line: Enabling Functional Validation

A crucial tool for the functional dissection of PTPRZ1's role was the ready-to-use NCI-H520 PTPRZ1 knockout cell line (CGKO-M2278). This precise genetic model provided by HySigen Bioscience was instrumental in two key phases of the study:

1. In Vitro Functional Proof: Utilizing the CGKO-M2278 cells, the team demonstrated thatloss of PTPRZ1 significantly impaired cancer cell proliferation andcolony-forming ability in functional assays.

2. In Vivo Causal Evidence: The knockout cells were used to establish xenograft models, where their use led to the critical finding that PTPRZ1 ablation resulted in dramatic tumor growth suppression (≈70% reduction), solidifying its essential role in LUSC tumorigenesis in vivo.

✨ Key Takeaway: The PTPRZ1-KO cell line served as a foundational tool, providing the clean genetic background necessary to definitively establish PTPRZ1 as a bona fide LUSC driver oncogene. This robust functional evidence was pivotal in validating the PTPRZ1-MDK axis as a promising new target for therapeutic intervention.

Publication: NingY Q, Wang J, Zhang Y, et al. Enhancer Reprogramming Reveals the Tumorigenic Role of PTPRZ1 in Lung Squamous Cell Carcinoma[J]. Advanced Science, 2025:e09344. https://doi.org/10.1002/advs.202509344‍

| ‍Ready-to-use Human PTPRZ1 knockout NCI-H520 cell line		‍
	Catalogue No.: CGKO-M2278
	Gene ID: 5803

| ‍Gene Knock-out Service	‍‍
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