1. Academic Validation
  2. CRKL is a critical target of Hh-GLI2 pathway in lung adenocarcinoma

CRKL is a critical target of Hh-GLI2 pathway in lung adenocarcinoma

  • J Cell Mol Med. 2021 Jun 2;25(13):6280-6288. doi: 10.1111/jcmm.16592.
Xiaoming Liu 1 Yan Hu 2 Bentong Yu 1 Kai Peng 1 Xin Gan 3
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, China.
  • 3 Department of Respiratory and Critical Care, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Abstract

Lung adenocarcinoma (LUAD) is one of the important components of non-small-cell lung Cancer (NSCLC) and leads to many deaths every year. During the initiation and progression of the LUAD, the Hh-GLI2 pathway plays critical roles. Several components of this pathway have been shown to be amplified or overexpressed in LUAD, providing this pathway as an attractive target for therapeutics. However, a gap in our understanding of the Hh-GLI2 pathway is the identity of transcriptional targets of GLI2 that drive LUAD tumorigenesis. Here, we show that the oncogene CRKL is a direct target of GLI2. GLI2 turns on CRKL transcription through binding its second intron. Furthermore, CRKL is an essential mediator for GLI2-driven proliferation and migration of LUAD cells. Depletion of CRKL blunts Hh-GLI2 pathway-mediated cell proliferation and invasion. Lastly, we find that CRKL knockout cells are more sensitive to EGFR-TKI and chemotherapeutics. Taken together, our work here identifies a specific target for Hh-related malignancies and provides CRKL as a promising therapeutic target for LUAD.

Keywords

CRKL; GLI2; Hh; LUAD.

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