CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling
Lung cancer is a malignancy with high mortality worldwide, and metastasis occurs at a high frequency even when cancer spread is not detectable at primary operation. Cancer stemness plays an important role in malignant cancer behavior, treatment resistance, and cancer metastasis. Therefore, understan...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/4057 |
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| author | Yen-Yun Wang Anupama Vadhan Ping-Ho Chen Yen-Lung Lee Chih-Yeh Chao Kuang-Hung Cheng Yu-Chiuan Chang Stephen Chu-Sung Hu Shyng-Shiou F. Yuan |
| author_facet | Yen-Yun Wang Anupama Vadhan Ping-Ho Chen Yen-Lung Lee Chih-Yeh Chao Kuang-Hung Cheng Yu-Chiuan Chang Stephen Chu-Sung Hu Shyng-Shiou F. Yuan |
| author_sort | Yen-Yun Wang |
| collection | DOAJ |
| description | Lung cancer is a malignancy with high mortality worldwide, and metastasis occurs at a high frequency even when cancer spread is not detectable at primary operation. Cancer stemness plays an important role in malignant cancer behavior, treatment resistance, and cancer metastasis. Therefore, understanding the molecular pathogenesis behind cancer-stemness-mediated metastasis and developing effective approaches to prevent metastasis are key issues for improving cancer treatment. In this study, we investigated the role of CD44 stemness marker in lung cancer using in vitro and clinical studies. Immunohistochemical staining of lung cancer tissue specimens revealed that primary tumors with higher CD44 expression showed increased metastasis to regional lymph nodes. Flow cytometry analysis suggested that CD44 positive cells were enriched in the metastatic lymph nodes compared to the primary tumors. CD44 overexpression significantly increased migration and invasion abilities of lung cancer cells through CD44-induced ERK phosphorylation, ZEB1 upregulation, and Claudin-1 downregulation. Furthermore, ERK inhibition suppressed the migration and invasion abilities of CD44-overexpressing lung cancer cells. In summary, our in vitro and clinical results indicate that CD44 may be a potential prognostic and therapeutic marker for lung cancer patients. |
| first_indexed | 2024-03-10T08:57:40Z |
| format | Article |
| id | doaj.art-8fefa576b2a04926b91e20e023529f6b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:57:40Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8fefa576b2a04926b91e20e023529f6b2023-11-22T07:03:08ZengMDPI AGCancers2072-66942021-08-011316405710.3390/cancers13164057CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 SignalingYen-Yun Wang0Anupama Vadhan1Ping-Ho Chen2Yen-Lung Lee3Chih-Yeh Chao4Kuang-Hung Cheng5Yu-Chiuan Chang6Stephen Chu-Sung Hu7Shyng-Shiou F. Yuan8Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanSchool of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDepartment of Mechanical Engineering, National Pingtung University of Science and Technology, Pingtung 912, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, TaiwanInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, TaiwanDepartment of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanTranslational Research Center, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanLung cancer is a malignancy with high mortality worldwide, and metastasis occurs at a high frequency even when cancer spread is not detectable at primary operation. Cancer stemness plays an important role in malignant cancer behavior, treatment resistance, and cancer metastasis. Therefore, understanding the molecular pathogenesis behind cancer-stemness-mediated metastasis and developing effective approaches to prevent metastasis are key issues for improving cancer treatment. In this study, we investigated the role of CD44 stemness marker in lung cancer using in vitro and clinical studies. Immunohistochemical staining of lung cancer tissue specimens revealed that primary tumors with higher CD44 expression showed increased metastasis to regional lymph nodes. Flow cytometry analysis suggested that CD44 positive cells were enriched in the metastatic lymph nodes compared to the primary tumors. CD44 overexpression significantly increased migration and invasion abilities of lung cancer cells through CD44-induced ERK phosphorylation, ZEB1 upregulation, and Claudin-1 downregulation. Furthermore, ERK inhibition suppressed the migration and invasion abilities of CD44-overexpressing lung cancer cells. In summary, our in vitro and clinical results indicate that CD44 may be a potential prognostic and therapeutic marker for lung cancer patients.https://www.mdpi.com/2072-6694/13/16/4057CD44lung cancerERKZEB1metastasis |
| spellingShingle | Yen-Yun Wang Anupama Vadhan Ping-Ho Chen Yen-Lung Lee Chih-Yeh Chao Kuang-Hung Cheng Yu-Chiuan Chang Stephen Chu-Sung Hu Shyng-Shiou F. Yuan CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling Cancers CD44 lung cancer ERK ZEB1 metastasis |
| title | CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling |
| title_full | CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling |
| title_fullStr | CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling |
| title_full_unstemmed | CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling |
| title_short | CD44 Promotes Lung Cancer Cell Metastasis through ERK–ZEB1 Signaling |
| title_sort | cd44 promotes lung cancer cell metastasis through erk zeb1 signaling |
| topic | CD44 lung cancer ERK ZEB1 metastasis |
| url | https://www.mdpi.com/2072-6694/13/16/4057 |
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