J Cancer 2019; 10(2):510-521. doi:10.7150/jca.26578 This issue

Research Paper

Lycopene upregulates ZO-1 and downregulates claudin-1 through autophagy inhibition in the human cutaneous squamous cell carcinoma cell line COLO-16

Suyun Bi1,2#, Li Li1#, Heng Gu1#, Min Li1#, Song Xu1, Wenbo Bu1, Mengli Zhang1, Zhihai Zhou2, Xu Chen1✉

1. Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, 210042, China
2. Dermatology and Venereology Department, Tianjin Medical University General Hospital, Tianjin, China.
# these authors contribute to this work equally.

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Bi S, Li L, Gu H, Li M, Xu S, Bu W, Zhang M, Zhou Z, Chen X. Lycopene upregulates ZO-1 and downregulates claudin-1 through autophagy inhibition in the human cutaneous squamous cell carcinoma cell line COLO-16. J Cancer 2019; 10(2):510-521. doi:10.7150/jca.26578. Available from https://www.jcancer.org/v10p0510.htm

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Lycopene, a kind of carotenoid, has been reported to have an inhibitory function on tumor cell migration. However, the potential role of lycopene in the treatment of cutaneous squamous cell carcinoma (cSCC) remains unclear. Therefore, we assessed the biological effects of lycopene in the human cSCC cell line COLO-16, human epidermal keratinocytes (HEKs) and the immortalized human keratinocyte cell line HaCaT. We found that lycopene inhibited the cell proliferation and migration of COLO-16 cells but not normal keratinocytes. In addition, lycopene upregulated the protein levels of ZO-1 in COLO-16 and HaCaT cells but not in HEKs. In contrast, lycopene upregulated the protein level of claudin-1 in HEKs but downregulated claudin-1 in COLO-16 cells. Lycopene led to a decrease in autophagic flux in COLO-16 cells in a mechanistic target of rapamycin complex 1 (MTORC1)-dependent manner. Importantly, autophagy inhibition contributed to the lycopene-induced regulation on ZO-1 and claudin-1 in COLO-16 cells. Moreover, JNK inhibitor (SP600125) and MEK inhibitor (U0126) treatment abolished the increase in phosphorylated MTOR and ribosomal protein S6 as well as the increase in ZO-1 and the decrease in claudin-1 in lycopene-treated COLO-16 cells. Gene silencing of JNK and ERK also prohibited ZO-1 upregulation and claudin-1 downregulation. In conclusion, lycopene upregulates ZO-1 expression and downregulates claudin-1 expression through the activation of ERK, JNK and MTORC1 as well as the inhibition of autophagy in human cSCC cells. Our findings demonstrate that autophagy plays a key role in lycopene-mediated pharmacological effects. This study indicates that lycopene might be a useful chemopreventive agent against cSCC.

Keywords: lycopene, cutaneous squamous cell carcinoma, keratinocyte, autophagy, tight junction