CLEC12B suppresses lung cancer progression by inducing SHP-1 expression and inactivating the PI3K/AKT signaling pathway

Journal Article · Wed Dec 15 04:00:00 EST 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112914· OSTI ID:23195277

Chi, Decai ^[1]; Wang, Dong ^[2]; Zhang, Minghui ^[3]; Ma, Hui ^[4]; Chen, Fuhui; Sun, Yajiao ^[2]

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1. Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086 (China)
2. Department of Respiratory Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086 (China)
3. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081 (China)
4. Harbin Medical University, Harbin, 150086 (China)

Lung cancer is the leading cause of cancer mortality worldwide. CLEC12B, a C-type lectin-like receptor, is low-expressed in lung cancer tissues. However, the function of CLEC12B in lung cancer and its underlying mechanism remain unclear. Here, an obvious down-regulation of CLEC12B was observed in lung cancer cells compared with the normal lung epithelial cells. CLEC12B over-expression suppressed cell viability and cell cycle entry in lung cancer, along with the reduction of PCNA and cyclin D1 expressions, while silencing CLEC12B possessed the opposite effects. Over-expression of CLEC12B promoted lung cancer cell apoptosis, accompanied by decreased Bcl-2 and increased Bax, cleaved caspase-3 and cleaved caspase-9. Moreover, CLEC12B decreased phosphorylation of PI3K-p85 and AKT proteins. By contrast, CLEC12B knockdown activated the PI3K/AKT pathway. In vivo, CLEC12B inhibited tumor growth in lung cancer, which can be reversed by CLEC12B inhibition. Co-IP and immunofluorescence assays confirmed the interaction between CLEC12B and SHP-1, and CLEC12B over-expression increased SHP-1 level. Furthermore, knocking down SHP-1 abrogated the above biological phenotypes caused by CLEC12B elevation. Taken together, our findings demonstrate that CLEC12B serves as a tumor-suppressing gene in lung cancer through positively regulating SHP-1 expression, which may be mediated by the PI3K/AKT signaling pathway.

• OSTI ID: 23195277
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 409; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
APOPTOSIS
CELL CYCLE
IN VIVO
LECTINS
LUNGS
MORTALITY
NEOPLASMS
PHENOTYPE
PHOSPHORYLATION
RECEPTORS