CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC
Cdc42-interacting protein 4 (CIP4), a member of the F-BAR family, which plays an important role in regulating cell membrane and actin, has been reported to interact with Cdc42 and be closely associated with tumor invadopodia formation. In this study, we found that CIP4 expression was significantly h...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-03-01
|
| Series: | Molecular Therapy: Oncolytics |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770522000407 |
| _version_ | 1819018033464606720 |
|---|---|
| author | Zhiyan Hu Jiaxian Zhu Yidan Ma Ting Long Lingfang Gao Yan Zhong Xiaoyan Wang Zuguo Li |
| author_facet | Zhiyan Hu Jiaxian Zhu Yidan Ma Ting Long Lingfang Gao Yan Zhong Xiaoyan Wang Zuguo Li |
| author_sort | Zhiyan Hu |
| collection | DOAJ |
| description | Cdc42-interacting protein 4 (CIP4), a member of the F-BAR family, which plays an important role in regulating cell membrane and actin, has been reported to interact with Cdc42 and be closely associated with tumor invadopodia formation. In this study, we found that CIP4 expression was significantly higher in human CRC tissues and correlated with the CRC infiltrating depth and metastasis, as well as the lower survival rate in patients. In cultured CRC cells, knockdown of CIP4 inhibited cell migration and invasion ability in vitro and tumor metastasis in vivo, while the overexpression of CIP4 promoted invadopodia formation and matrix degradation ability. We then identified GTP-Cdc42 as a directly interactive protein of CIP4, which was upregulated and recruited by CIP4. Furthermore, activated NF-κB signaling pathway was found in CIP4 overexpression of CRC cells contributing to invadopodia formation, while the inhibition of either CIP4 or Cdc42 led to the suppression of the NF-κB pathway and resulted in a decreased quantity of invadopodia. Our findings suggested that CIP4 targets to recruit GTP-Cdc42 and directly combines with it to accelerate invadopodia formation and function by activating NF-κB signaling pathway, thus promoting CRC infiltration and metastasis. |
| first_indexed | 2024-12-21T03:12:59Z |
| format | Article |
| id | doaj.art-cac3f744a8a64d1abf8081a6b450c7dc |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-21T03:12:59Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-cac3f744a8a64d1abf8081a6b450c7dc2022-12-21T19:17:55ZengElsevierMolecular Therapy: Oncolytics2372-77052022-03-0124873886CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRCZhiyan Hu0Jiaxian Zhu1Yidan Ma2Ting Long3Lingfang Gao4Yan Zhong5Xiaoyan Wang6Zuguo Li7Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, 510515 Guangdong Province, P.R. ChinaDepartment of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 Guangdong Province, P.R. China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. ChinaDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, 510515 Guangdong Province, P.R. ChinaDepartment of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 Guangdong Province, P.R. ChinaDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 Guangdong Province, P.R. ChinaDepartment of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 Guangdong Province, P.R. ChinaDepartment of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Guangdong Provincial Key Laboratory of Molecular Tumour Pathology, Guangzhou, 510515 Guangdong Province, P.R. ChinaDepartment of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 Guangdong Province, P.R. China; The Third School of Clinical Medicine, Southern Medical University, Guangzhou, 510515 Guangdong Province, P.R. China; Corresponding author Zuguo Li, Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518101 Guangdong Province, P.R. China.Cdc42-interacting protein 4 (CIP4), a member of the F-BAR family, which plays an important role in regulating cell membrane and actin, has been reported to interact with Cdc42 and be closely associated with tumor invadopodia formation. In this study, we found that CIP4 expression was significantly higher in human CRC tissues and correlated with the CRC infiltrating depth and metastasis, as well as the lower survival rate in patients. In cultured CRC cells, knockdown of CIP4 inhibited cell migration and invasion ability in vitro and tumor metastasis in vivo, while the overexpression of CIP4 promoted invadopodia formation and matrix degradation ability. We then identified GTP-Cdc42 as a directly interactive protein of CIP4, which was upregulated and recruited by CIP4. Furthermore, activated NF-κB signaling pathway was found in CIP4 overexpression of CRC cells contributing to invadopodia formation, while the inhibition of either CIP4 or Cdc42 led to the suppression of the NF-κB pathway and resulted in a decreased quantity of invadopodia. Our findings suggested that CIP4 targets to recruit GTP-Cdc42 and directly combines with it to accelerate invadopodia formation and function by activating NF-κB signaling pathway, thus promoting CRC infiltration and metastasis.http://www.sciencedirect.com/science/article/pii/S2372770522000407CIP4Cdc42NF-κBinvadopodiacolorectal cancerinvasion |
| spellingShingle | Zhiyan Hu Jiaxian Zhu Yidan Ma Ting Long Lingfang Gao Yan Zhong Xiaoyan Wang Zuguo Li CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC Molecular Therapy: Oncolytics CIP4 Cdc42 NF-κB invadopodia colorectal cancer invasion |
| title | CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC |
| title_full | CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC |
| title_fullStr | CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC |
| title_full_unstemmed | CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC |
| title_short | CIP4 targeted to recruit GTP-Cdc42 involving in invadopodia formation via NF-κB signaling pathway promotes invasion and metastasis of CRC |
| title_sort | cip4 targeted to recruit gtp cdc42 involving in invadopodia formation via nf κb signaling pathway promotes invasion and metastasis of crc |
| topic | CIP4 Cdc42 NF-κB invadopodia colorectal cancer invasion |
| url | http://www.sciencedirect.com/science/article/pii/S2372770522000407 |
| work_keys_str_mv | AT zhiyanhu cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc AT jiaxianzhu cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc AT yidanma cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc AT tinglong cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc AT lingfanggao cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc AT yanzhong cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc AT xiaoyanwang cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc AT zuguoli cip4targetedtorecruitgtpcdc42involvingininvadopodiaformationvianfkbsignalingpathwaypromotesinvasionandmetastasisofcrc |