RAB14 activates MARK signaling to promote bladder tumorigenesis

Haichao Chao, Leihong Deng, Fanghua Xu, Bin Fu, Zunwei Zhu, Zhifeng Dong, Yen-Nien Liu, Tao Zeng

Research output: Contribution to journalArticle

Abstract

Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential, and its abundance was significantly associated with lymph node metastasis (p=0.001), a high-grade tumor stage (p=0.009), poor differentiation (p<0.001), and unfavorable prognoses of BC patients (p=0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein, and inhibited cell migration and invasion (p<0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling through upregulation of MAPK1/MAPK8 and downregulation of DUSP6/SHC1/FOS. We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.

Original languageEnglish
JournalCarcinogenesis
DOIs
Publication statusE-pub ahead of print - Feb 27 2019

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Urinary Bladder Neoplasms
Carcinogenesis
Urinary Bladder
Mitogen-Activated Protein Kinases
Twist-Related Protein 1
Neoplasms
Extracellular Signal-Regulated MAP Kinases
Heterografts
Carcinogens
Cell Movement
Up-Regulation
Down-Regulation
Lymph Nodes
Cell Proliferation
Apoptosis
Neoplasm Metastasis

Cite this

Chao, H., Deng, L., Xu, F., Fu, B., Zhu, Z., Dong, Z., ... Zeng, T. (2019). RAB14 activates MARK signaling to promote bladder tumorigenesis. Carcinogenesis. https://doi.org/10.1093/carcin/bgz039

RAB14 activates MARK signaling to promote bladder tumorigenesis. / Chao, Haichao; Deng, Leihong; Xu, Fanghua; Fu, Bin; Zhu, Zunwei; Dong, Zhifeng; Liu, Yen-Nien; Zeng, Tao.

In: Carcinogenesis, 27.02.2019.

Research output: Contribution to journalArticle

Chao, Haichao ; Deng, Leihong ; Xu, Fanghua ; Fu, Bin ; Zhu, Zunwei ; Dong, Zhifeng ; Liu, Yen-Nien ; Zeng, Tao. / RAB14 activates MARK signaling to promote bladder tumorigenesis. In: Carcinogenesis. 2019.
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abstract = "Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5{\%} of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential, and its abundance was significantly associated with lymph node metastasis (p=0.001), a high-grade tumor stage (p=0.009), poor differentiation (p<0.001), and unfavorable prognoses of BC patients (p=0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein, and inhibited cell migration and invasion (p<0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling through upregulation of MAPK1/MAPK8 and downregulation of DUSP6/SHC1/FOS. We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.",
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AU - Deng, Leihong

AU - Xu, Fanghua

AU - Fu, Bin

AU - Zhu, Zunwei

AU - Dong, Zhifeng

AU - Liu, Yen-Nien

AU - Zeng, Tao

N1 - © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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N2 - Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential, and its abundance was significantly associated with lymph node metastasis (p=0.001), a high-grade tumor stage (p=0.009), poor differentiation (p<0.001), and unfavorable prognoses of BC patients (p=0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein, and inhibited cell migration and invasion (p<0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling through upregulation of MAPK1/MAPK8 and downregulation of DUSP6/SHC1/FOS. We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.

AB - Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential, and its abundance was significantly associated with lymph node metastasis (p=0.001), a high-grade tumor stage (p=0.009), poor differentiation (p<0.001), and unfavorable prognoses of BC patients (p=0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein, and inhibited cell migration and invasion (p<0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling through upregulation of MAPK1/MAPK8 and downregulation of DUSP6/SHC1/FOS. We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.

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