TY - JOUR
T1 - CAMSAP2 enhances lung cancer cell metastasis by mediating RASAL2 degradation
AU - Singharajkomron, Natsaranyatron
AU - Yodsurang, Varalee
AU - Limprasutr, Vudhiporn
AU - Wattanathamsan, Onsurang
AU - Iksen, Iksen
AU - Hayakawa, Yoshihiro
AU - Pongrakhananon, Varisa
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/2/1
Y1 - 2024/2/1
N2 - Aims: Cancer metastasis significantly contributes to mortality in lung cancer patients. Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2) plays a significant role in cancer cell migration; however, its role in lung cancer metastasis and the underlying mechanism remain largely unknown. The present study aimed to investigate the impact of CAMSAP2 on lung cancer. Main methods: The clinical relevance of CAMSAP2 in lung cancer patients was assessed using public database. RNA interference experiments were conducted to investigate role of CAMSAP2 in cell migration through transwell and wound healing assays. Molecular mechanisms were explored by identifying the possible interacting partners and pathways using the BioGRID and KEGG pathway analyses. The impact of CAMSAP2 on Ras protein activator-like 2 (RASAL2)-mediated lung cancer metastasis was investigated through biochemical assays. Additionally, in vivo experimentation using a murine tail vein metastasis model was performed to comprehend CAMSAP2's influence on metastasis. Key findings: A high expression level of CAMSAP2 was associated with poor overall survival in lung cancer patients and it positively correlated with cell migration in non-small cell lung cancer (NSCLC) cell lines. Knockdown of CAMSAP2 inhibited lung cancer cell motility in vitro and metastasis in vivo. Proteomic and biochemical analyses revealed the interaction between CAMSAP2 and RASAL2, which facilitates the degradation of RASAL2 through the ubiquitin–proteasome system. These degradation processes resulted in the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby promoting lung cancer metastasis. Collectively, the results of this study suggest that CAMSAP2 is a crucial regulator of cancer cell migration and metastasis and a promising therapeutic target for lung cancer.
AB - Aims: Cancer metastasis significantly contributes to mortality in lung cancer patients. Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2) plays a significant role in cancer cell migration; however, its role in lung cancer metastasis and the underlying mechanism remain largely unknown. The present study aimed to investigate the impact of CAMSAP2 on lung cancer. Main methods: The clinical relevance of CAMSAP2 in lung cancer patients was assessed using public database. RNA interference experiments were conducted to investigate role of CAMSAP2 in cell migration through transwell and wound healing assays. Molecular mechanisms were explored by identifying the possible interacting partners and pathways using the BioGRID and KEGG pathway analyses. The impact of CAMSAP2 on Ras protein activator-like 2 (RASAL2)-mediated lung cancer metastasis was investigated through biochemical assays. Additionally, in vivo experimentation using a murine tail vein metastasis model was performed to comprehend CAMSAP2's influence on metastasis. Key findings: A high expression level of CAMSAP2 was associated with poor overall survival in lung cancer patients and it positively correlated with cell migration in non-small cell lung cancer (NSCLC) cell lines. Knockdown of CAMSAP2 inhibited lung cancer cell motility in vitro and metastasis in vivo. Proteomic and biochemical analyses revealed the interaction between CAMSAP2 and RASAL2, which facilitates the degradation of RASAL2 through the ubiquitin–proteasome system. These degradation processes resulted in the activation of the extracellular signal-regulated kinase (ERK) signaling pathway, thereby promoting lung cancer metastasis. Collectively, the results of this study suggest that CAMSAP2 is a crucial regulator of cancer cell migration and metastasis and a promising therapeutic target for lung cancer.
KW - Calmodulin-regulated spectrin-associated protein family member 2 (CAMSAP2)
KW - Cell migration
KW - Extracellular signal-regulated kinase (ERK)
KW - Metastasis
KW - Proteasome
KW - Ras protein activator like 2 (RASAL2)
UR - http://www.scopus.com/inward/record.url?scp=85181053095&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2023.122391
DO - 10.1016/j.lfs.2023.122391
M3 - 学術論文
C2 - 38159595
AN - SCOPUS:85181053095
SN - 0024-3205
VL - 338
JO - Life Sciences
JF - Life Sciences
M1 - 122391
ER -