HSPA1L Enhances Cancer Stem Cell-Like Properties by Activating IGF1Rβ and Regulating β-Catenin Transcription
| Autor: | In-Gyu Kim, Rae-Kwon Kim, Soo-Im Choi, Yeon-Jee Kahm, Eun-Wie Cho, Uhee Jung, Jei-Ha Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
cancer stem cell
Lung Neoplasms Transcription Genetic Integrin Article Catalysis Receptor IGF Type 1 Metastasis lcsh:Chemistry Inorganic Chemistry Transcription (biology) Cancer stem cell Carcinoma Non-Small-Cell Lung medicine Humans HSP70 Heat-Shock Proteins HSPA1L Physical and Theoretical Chemistry ALDH1 lcsh:QH301-705.5 Molecular Biology Protein kinase B beta Catenin Spectroscopy biology Chemistry Organic Chemistry EMT Promoter General Medicine β-catenin medicine.disease Neoplasm Proteins Computer Science Applications Cell biology lcsh:Biology (General) lcsh:QD1-999 A549 Cells Catenin Neoplastic Stem Cells biology.protein |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 18 International Journal of Molecular Sciences, Vol 21, Iss 6957, p 6957 (2020) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms21186957 |
| Popis: | Studies have shown that cancer stem cells (CSCs) are involved in resistance and metastasis of cancer thus, therapies targeting CSCs have been proposed. Here, we report that heat shock 70-kDa protein 1-like (HSPA1L) is partly involved in enhancing epithelial&ndash mesenchymal transition (EMT) and CSC-like properties in non-small cell lung cancer (NSCLC) cells. Aldehyde dehydrogenase 1 (ALDH1) is considered a CSC marker in some lung cancers. Here, we analyzed transcriptional changes in genes between ALDH1high and ALDH1low cells sorted from A549 NSCLC cells and found that HSPA1L was highly expressed in ALDH1high cells. HSPA1L played two important roles in enhancing CSC-like properties. First, HSPA1L interacts directly with IGF1R&beta and integrin &alpha V to form a triple complex that is involved in IGF1R&beta activation. HSPA1L/integrin &alpha V complex-associated IGF1R&beta activation intensified the EMT-associated cancer stemness and &gamma radiation resistance through its downstream AKT/NF-&kappa B or AKT/GSK3&beta /&beta catenin activation pathway. Secondly, HSPA1L was also present in the nucleus and could bind directly to the promoter region of &beta catenin to function as a transcription activator of &beta catenin, an important signaling protein characterizing CSCs by regulating ALDH1 expression. HSPA1L may be a novel potential target for cancer treatment because it both enhances IGF1R&beta activation and regulates &gamma &beta catenin transcription, accumulating CSC-like properties. |
| Databáze: | OpenAIRE |
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