Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10

Hung, Ming-Szu; Chen, Yi-Chuan; Lin, Paul-Yann; Li, Ya-Chin; Hsu, Chia-Chen; Lung, Jr-Hau; You, Liang; Xu, Zhidong; Mao, Jian-Hua; Jablons, David M.; Yang, Cheng-Ta

doi:10.3390/cancers11050618

Title: Cul4A Modulates Invasion and Metastasis of Lung Cancer through Regulation of ANXA10

Journal Article · Thu May 02 00:00:00 EDT 2019 · Cancers (Basel)

DOI:https://doi.org/10.3390/cancers11050618· OSTI ID:1637291

Hung, Ming-Szu ^[1]; Chen, Yi-Chuan ^[2]; Lin, Paul-Yann ^[3]; Li, Ya-Chin ^[2]; Hsu, Chia-Chen ^[2]; Lung, Jr-Hau ^[2]; You, Liang ^[4]; Xu, Zhidong ^[4];

^[5]; Jablons, David M. ^[4]; Yang, Cheng-Ta ^[6]

Chang Gung Memorial Hospital, Chiayi (Taiwan); Chang Gung University, Taoyuan (Taiwan); Chang Gung University of Science and Technology, Chiayi (Taiwan)
Chang Gung Memorial Hospital, Chiayi (Taiwan)
Buddhist Tzu Chi Medical Foundation, Chiayi (Taiwan)
Univ. of California, San Francisco, CA (United States)
Chang Gung University, Taoyuan (Taiwan)
Chang Gung University, Taoyuan (Taiwan); Chang Gung Memorial Hospital, Taoyuan (Taiwan)

Cullin 4A (Cul4A) is overexpressed in a number of cancers and has been established as an oncogene. This study aimed to elucidate the role of Cul4A in lung cancer invasion and metastasis. We observed that Cul4A was overexpressed in non-small cell lung cancer (NSCLC) tissues and the overexpression of Cul4A was associated with poor prognosis after surgical resection and it also decreased the expression of the tumor suppressor protein annexin A10 (ANXA10). The knockdown of Cul4A was associated with the upregulation of ANXA10, and the forced expression of Cul4A was associated with the downregulation of ANXA10 in lung cancer cells. Further studies showed that the knockdown of Cul4A inhibited the invasion and metastasis of lung cancer cells, which was reversed by the further knockdown of ANXA10. In addition, the knockdown of Cul4A inhibited lung tumor metastasis in mouse tail vein injection xenograft models. Notably, Cul4A regulated the degradation of ANXA10 through its interaction with ANXA10 and ubiquitination in lung cancer cells. Our findings suggest that Cul4A is a prognostic marker in NSCLC patients, and Cul4A plays important roles in lung cancer invasion and metastasis through the regulation of the ANXA10 tumor suppressor.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC); Chang Gung Memorial Hospital; National Science Council, Taiwan

Grant/Contract Number:: AC02-05CH11231; CMRPG6F0221; CORPG6F0042; CMRPG6G0031; 101-2314-B-182-086-MY2

OSTI ID:: 1637291

Journal Information:: Cancers (Basel), Vol. 11, Issue 5; ISSN 2072-6694

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 15 works

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