CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells
Some cancer cells migration and metastasis are characterized by the outgrowth of lamellipodia protrusions in which the underlying mechanism remains unclear. Evidence has confirmed that lamellipodia formation could be regulated by various adhesion molecules, such as CD44, and we previously reported t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1224827/full |
| _version_ | 1797671354914308096 |
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| author | Yaqi Qiu Yaqi Qiu Hui Wang Hui Wang Qian Guo Yiwen Liu Yiqing He Guoliang Zhang Cuixia Yang Cuixia Yang Yan Du Feng Gao Feng Gao |
| author_facet | Yaqi Qiu Yaqi Qiu Hui Wang Hui Wang Qian Guo Yiwen Liu Yiqing He Guoliang Zhang Cuixia Yang Cuixia Yang Yan Du Feng Gao Feng Gao |
| author_sort | Yaqi Qiu |
| collection | DOAJ |
| description | Some cancer cells migration and metastasis are characterized by the outgrowth of lamellipodia protrusions in which the underlying mechanism remains unclear. Evidence has confirmed that lamellipodia formation could be regulated by various adhesion molecules, such as CD44, and we previously reported that lamellipodia at the leading edge of luminal type breast cancer (BrCa) were enriched with high expression of CD44. In this study, we found that the overexpression of CD44s could promote lamellipodia formation in BrCa cells through inducing tissue type plasminogen activator (tPA) upregulation, which was achieved by PI3K/Akt signaling pathway activation. Moreover, we revealed that tPA could interact with LDL receptor related protein 1 (LRP1) to activate the downstream NFκB signaling pathway, which in turn facilitate lamellipodia formation. Notably, inhibition of the tPA/LRP1-NFkB signaling cascade could attenuate the CD44s-induced lamellipodia formation. Thus, our findings uncover a novel role of CD44s in driving lamellipodia outgrowth through tPA/LRP1-NFkB axis in luminal BrCa cells that may be helpful for seeking potential therapeutic targets. |
| first_indexed | 2024-03-11T21:14:10Z |
| format | Article |
| id | doaj.art-c19996043bf84c6da73f2234f92a9774 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-11T21:14:10Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-c19996043bf84c6da73f2234f92a97742023-09-29T05:33:58ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-09-011110.3389/fcell.2023.12248271224827CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cellsYaqi Qiu0Yaqi Qiu1Hui Wang2Hui Wang3Qian Guo4Yiwen Liu5Yiqing He6Guoliang Zhang7Cuixia Yang8Cuixia Yang9Yan Du10Feng Gao11Feng Gao12Department of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Molecular Biology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSome cancer cells migration and metastasis are characterized by the outgrowth of lamellipodia protrusions in which the underlying mechanism remains unclear. Evidence has confirmed that lamellipodia formation could be regulated by various adhesion molecules, such as CD44, and we previously reported that lamellipodia at the leading edge of luminal type breast cancer (BrCa) were enriched with high expression of CD44. In this study, we found that the overexpression of CD44s could promote lamellipodia formation in BrCa cells through inducing tissue type plasminogen activator (tPA) upregulation, which was achieved by PI3K/Akt signaling pathway activation. Moreover, we revealed that tPA could interact with LDL receptor related protein 1 (LRP1) to activate the downstream NFκB signaling pathway, which in turn facilitate lamellipodia formation. Notably, inhibition of the tPA/LRP1-NFkB signaling cascade could attenuate the CD44s-induced lamellipodia formation. Thus, our findings uncover a novel role of CD44s in driving lamellipodia outgrowth through tPA/LRP1-NFkB axis in luminal BrCa cells that may be helpful for seeking potential therapeutic targets.https://www.frontiersin.org/articles/10.3389/fcell.2023.1224827/fullCD44TPAlamellipodialuminal type breast cancerLRP1 |
| spellingShingle | Yaqi Qiu Yaqi Qiu Hui Wang Hui Wang Qian Guo Yiwen Liu Yiqing He Guoliang Zhang Cuixia Yang Cuixia Yang Yan Du Feng Gao Feng Gao CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells Frontiers in Cell and Developmental Biology CD44 TPA lamellipodia luminal type breast cancer LRP1 |
| title | CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells |
| title_full | CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells |
| title_fullStr | CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells |
| title_full_unstemmed | CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells |
| title_short | CD44s-activated tPA/LRP1-NFκB pathway drives lamellipodia outgrowth in luminal-type breast cancer cells |
| title_sort | cd44s activated tpa lrp1 nfκb pathway drives lamellipodia outgrowth in luminal type breast cancer cells |
| topic | CD44 TPA lamellipodia luminal type breast cancer LRP1 |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1224827/full |
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