CD151 drives cancer progression depending on integrin α3β1 through EGFR signaling in non-small cell lung cancer.

Abstract

BACKGROUND:

Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion.

METHODS:

First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied.

RESULTS:

High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs.

CONCLUSIONS:

Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment.

• Authors: Jianjie Zhu, Tingting Cai, Jieqi Zhou, Wenwen Du, Yuanyuan Zeng, Ting Liu, Yulong Fu, Yue Li, Qian Qian, Xiuwei H Yang, Qinglin Li, Jian-An Huang, Zeyi Liu
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 40 Issue 1 Pg. 192 (Jun 09 2021) ISSN: 1756-9966 [Electronic] England
• PMID: 34108040 (Publication Type: Journal Article)

Chemical References

• CD151 protein, human
• Integrin alpha3beta1
• Tetraspanin 24

Topics

• A549 Cells
• Animals
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Disease Progression
• Female
• Heterografts
• Humans
• Immunohistochemistry
• Integrin alpha3beta1 (metabolism)
• Lung Neoplasms (genetics, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Signal Transduction
• Tetraspanin 24 (metabolism)
• Transfection