Effects of Galectin-1 on Biological Behavior in Cervical Cancer

Abstract

Background:We previously revealed that the expression of galectin-1 (LGALS1) was significantly reduced after neoadjuvant chemotherapy treatment in cervical cancer patients. The objective of this study is to investigate the effects of LGALS1 expression on biological behaviors of cervical cancer cells. Methods: Immunohistochemistry and immunocytochemistry were performed to detect the expression of LGALS1 in cervical cancer tissues and cells (SiHa and C33A). Western blot analysis was performed to evaluate the efficacy of lentivirus-mediated upregulation or downregulation of LGALS1 in cervical cancer cells. Cell viability and proliferation were detected by CCK-8 and BrdU assays, respectively. Annexin V-FITC/PI apoptosis detection kit was employed to measure the apoptosis of cervical cancer cells. Transwell invasion and migration assays were also conducted to explore the invasive and migratory capabilities of cervical cancer cells. The expression of apoptosis-(Bcl-2 and Bax), invasion-(MMP-2 and MMP-9), and migration-related (Fascin and Ezrin) proteins, were detected by Western blot analysis. Xenograft mouse model of cervical cancer was generated to explore whether LGALS1 overexpression could promote tumor growth in vivo. Results:LGALS1 was overexpressed in cervical cancer tissues and cell lines compared to that in normal cervical tissues and epithelium cells. Upregulation of LGALS1 significantly promoted the cell proliferation, inhibited cell apoptosis, and enhanced the migratory and invasive abilities of both SiHa and C33A cells, whereas downregulation of LGALS1 led to the opposite results. The level of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin expression was significantly upregulated in cervical cancer cells with LGALS1 overexpression, while converse results were obtained in LGALS1 knockdown cancer cells. In vivo study also showed that LGALS1 overexpression facilitated tumor growth of cervical cancer cells. Conclusion: Overexpression of LGALS1 significantly promoted and enhanced the aggressive features of cervical cancer both in vitro and in vivo, which may be associated with high expression of Bcl-2, MMP-2, MMP-9, Fascin, and Erzin proteins.

Ezrin Mediates Invasion and Metastasis in Tumorigenesis: A Review

“…LGALS1, Galectin-3, E-cadherin, MAPK JNK/p38 and Akt/ERK1/2 signaling Controls cell adhesion and enhances invasion. Serves as the cervical cancer marker for non-invasive detection Elliott et al, 2005;Saito et al, 2013;Kong et al, 2016;Fadiel et al, 2017;Li et al, 2017;Zacapala-Gomez et al, 2018;Chetry et al, 2020 Gastric cancer miR-183 Antagonizes mi-183 actions, and is correlated with tumor size, invasion lymph node and metastasis Li et al, 2011;Cao et al, 2014 Osteosarcoma miR-183, Akt and MAPK, Akt/mTOR Promotes tumor metastasis. High expression is correlated with poor prognosis Khanna et al, 2004;Krishnan et al, 2006 Hepatocellular cancer…”

“…Cervical cancer is generally caused by an infection of the human papillomavirus (HPV) (Saavedra et al, 2012). As a migration-related protein, Ezrin is upregulated in cervical cancer (Zacapala-Gomez et al, 2018;Chetry et al, 2020) and its expression level is associated with advanced metastasis and poor prognosis. Specifically, Ezrin is increased in cervical cancer cells (SiHa and C33A) when Galectin-1 (LGALS1) is overexpressed.…”

“…LGALS1 may interact with Ezrin through the MAPK, JNK/p38, and Akt/ERK1/2 pathways in the regulation of invasion and migration (Elliott et al, 2005;Chetry et al, 2020). Another lectin family member, Galectin-3, is also overexpressed along with Ezrin in cervical cancer and both are predictors of poor prognosis in cervical cancer patients (Li et al, 2017).…”

“…Ezrin expression is significantly suppressed when LGALS1 is downregulated. LGALS1 belongs to the carbohydrate-binding protein family and exhibits a high affinity for β-galactoside-containing glycol-conjugates ( Chetry et al, 2020 ). Although multiple signaling pathways linked to LGALS1 have been reported, the underlying mechanisms of how LGALS1 affects Ezrin levels have not been fully elucidated.…”

“…Although multiple signaling pathways linked to LGALS1 have been reported, the underlying mechanisms of how LGALS1 affects Ezrin levels have not been fully elucidated. LGALS1 may interact with Ezrin through the MAPK, JNK/p38, and Akt/ERK1/2 pathways in the regulation of invasion and migration ( Elliott et al, 2005 ; Chetry et al, 2020 ). Another lectin family member, Galectin-3, is also overexpressed along with Ezrin in cervical cancer and both are predictors of poor prognosis in cervical cancer patients ( Li et al, 2017 ).…”