ARPC4 promotes bladder cancer cell invasion and is associated with lymph node metastasis

• Published in: Journal of cellular biochemistry Vol. 121; no. 1; pp. 231 - 243
• Main Authors: Xu, Ning, Qu, Gen‐Yi, Wu, Yu‐Peng, Lin, Yun‐Zhi, Chen, Dong‐Ning, Li, Xiao‐Dong, Chen, Shao‐Hao, Huang, Jin‐Bei, Zheng, Qing‐Shui, Xue, Xue‐Yi, Wei, Yong
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2020
• Subjects: Actin; Actin Cytoskeleton - metabolism; Actins - metabolism; actin‐related protein 2/3 complex subunit 4; Adult; Aged; Bladder; Bladder cancer; Cancer; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Correlation analysis; Cystectomy; Cytoskeleton; Female; Gene expression; Health risk assessment; Humans; Immunofluorescence; invasion; metastasis; Invasiveness; lymph node metastasis; Lymph nodes; Lymphatic Metastasis; Lymphatic system; Male; Metastases; Metastasis; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Proteins; Pseudopodia; Risk analysis; Risk Factors; RNA, Small Interfering - metabolism; siRNA; Tissue Array Analysis; Tissues; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - surgery; Wound Healing; invasion; metastasis; bladder cancer; actin-related protein 2/3 complex subunit 4; lymph node metastasis
• ISSN: 0730-2312; 1097-4644; 1097-4644
• DOI: 10.1002/jcb.29136

The significance of actin‐related protein 2/3 complex subunit 4 (ARPC4) expression in bladder cancer, and its potential role in the invasion and migration of bladder cancer cells, has yet to be determined. This study was to identify the correlation between ARPC4 and lymph node metastasis, and to determine the role of ARPC4 in the invasive migration of T24 bladder cancer cells. One hundred and ninety‐eight bladder cancer tissues and 40 normal bladder and lymph node tissues were examined. Tissue microarrays were constructed and subjected to immunohistochemical stating for ARPC4. Multiple logistic analysis was used to determine risk factors associated with bladder cancer metastasis. ARPC4 expression in T24 bladder cancer cells was suppressed using small interfering RNA and changes in protein levels were determined by Western blot analysis. The proliferation of bladder cancer cells after knocking down of ARPC4 was determined by cell counting kit‐8. The effects of ARPC4 knockdown on T24 cell invasion and migration was determined using transwell and wound healing assays. Immunofluorescence analysis was performed to examine changes in pseudopodia formation and actin cytoskeleton structure. The expression of ARPC4 was elevated in bladder cancer tissues than normal tissues (84.3% vs 27.5%, P < 0.001). The multivariate logistic analysis demonstrated that the level of ARPC4, as a risk factor, was correlated with lymphatic metastasis (P < 0.05). ARPC4 knockdown attenuated proliferation, migration, invasion, and pseudopodia formation in T24 cells. ARPC4 expression, as a risk factor, is associated with lymphatic metastasis and is upregulated in bladder cancer tissues in comparison with normal tissues. Inhibition of ARPC4 expression significantly attenuates the proliferation, migration, and invasion of bladder cancer cell, possibly due to defects in pseudopodia formation. The objective of this study was to identify the correlation between actin‐related protein 2/3 complex subunit 4 (ARPC4) and lymph node metastasis, and to examine the role of ARPC4 in the invasive migration of T24 bladder cancer cells. Finally, we found that the expression of ARPC4, as a risk factor, was associated with lymphatic metastasis and was elevated in bladder cancer tissues when compared with normal bladder tissues. Besides, inhibition of ARPC4 expression significantly attenuated bladder cancer cell proliferation, migration, and invasion, possibly as a consequence of defects in pseudopodia formation.