J Cancer 2020; 11(18):5413-5423. doi:10.7150/jca.39760

Research Paper

Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4

Ya-Jing Yuan1*, Yao Sun2*, Rong Gao3, Zhen-zhen Yin2, Zhi-yong Yuan2✉, Li-Ming Xu2,4✉

1. Department of Anesthesia, Tianjin medical university cancer institute & hospital, National clinical research center for cancer, Key laboratory of cancer prevention and therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China.
2. Department of Radiation Oncology, Tianjin medical university cancer institute & hospital, National clinical research center for cancer, Key laboratory of Cancer Prevention and Therapy, Tianjin's clinical research center for cancer, Tianjin, 300060, China.
3. Department of Pathology, Gansu Medical College, Pingliang City, Gansu Province, 744000, China.
4. Department of Radiation Oncology, Tianjin Medical University Cancer Hospital airport hospital, Tianjin, 300308, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Yuan YJ, Sun Y, Gao R, Yin Zz, Yuan Zy, Xu LM. Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4. J Cancer 2020; 11(18):5413-5423. doi:10.7150/jca.39760. Available from https://www.jcancer.org/v11p5413.htm

File import instruction

Abstract

Lung cancer is a type of malignant tumor with high morbidity and mortality. Due to its complicated etiology and clinical manifestations, no significant therapeutic advance has been made. Lung squamous cell carcinoma (LSCC) is the most common type of lung cancer. To combat this disease, novel therapeutic targets are badly requirement. ASPM (Abnormal spindle-like microcephaly-associated protein) is involved in multiple cellular or developmental processes, such as neurogenesis and brain growth. ASPM is also reported widely expressed in multiple tumor tissues and involved in the development and progression of several cancers including lung cancer. However, the potential role on ASPM on LSCC is still unclear. In this study, we reported that ASPM was related to the poor prognosis of patients with lung squamous cell carcinoma. Our results further showed that ASPM depletion dramatically inhibited the proliferation of LSCC cells, consistent with the obviously decreased of cyclin D1(CCND1) and cyclin dependent kinases 4 (CDK4) expression. In vivo assays further confirmed ASPM ablation markedly blocked tumor growth in vivo compared with control. In addition, a co-expression was found between ASPM and CDK4 in human tumor tissues. Taken together, our data provides strong evidence that ASPM promotes lung squamous cell carcinoma proliferation in vitro and in vivo, and indicates its potential role as a LSCC therapeutic target.

Keywords: Lung squamous cell carcinoma, Proliferation, ASPM, CDK4, Therapeutic target