LHX6 inhibits breast cancer cell proliferation and invasion via repression of the Wnt/β-catenin signaling pathway

Abstract

Abstract. LIM homeobox domain 6 (LHX6), a member of the LHX family of proteins, has been implicated in cancer development. However, the involvement of LHX6 in the development of breast cancer remains unclear. In the present study, the epigenetic regulation, biological function and associated molecular mechanisms of LHX6 in breast cancer were analyzed. The expression levels of LHX6 were demonstrated to be markedly decreased in breast cancer tissues and cell lines. In addition, it was found that increased LHX6 expression in breast cancer cell lines inhibited cell proliferation and invasion. Furthermore, increased LHX6 expression significantly decreased the expression of β-catenin in MDA-MB-231 breast cancer cells, and small interfering RNA-β-catenin enhanced LHX6-induced inhibition of cell proliferation and invasion in MDA-MB-231 breast cancer cells. These results indicate that LHX6 inhibits breast cancer cell growth and invasion through suppression of the Wnt/β-catenin signaling pathway. Thus, the present study provides a novel insight into the underlying mechanism of tumorigenesis in breast cancer, indicating the therapeutic potential of LHX6 in the treatment of breast cancer.

Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression

“…LHX6 was reported to suppress the growth and invasion of breast cancer cells through inhibiting Wnt/β‑catenin signaling pathway 31 , and has been putatively identified as a tumor suppressor gene in lung cancer through regulating apoptosis-related genes p53 and Bcl-2, cell cycle-related gene p21 and cell proliferation-associated genes cyclinD1 and c-myc 32 . Since LHX6 was found to promote normal palate development through mediating cell cycle 33 , it is hypothesized that LHX6 may overcome the resistance to EGFR-TKIs in NSCLC through mediating the expression of cell cycle-, apoptosis- and proliferation-associated genes.…”

“…For example, LHX1, LHX2 and LHX4 have been identified as oncogenes of nephroblastoma, clear cell renal cell carcinoma, chronic myeloid leukemia, and acute lymphoblastic leukemia, and LHX3, LHX5 and LHX6 were considered methylation biomarkers of breast cancer, head and neck squamous cell carcinoma and cervical cancer, while LHX9 and LMX1 A were recognized as tumor-suppressor genes of pediatric malignant astrocytomas, follicular lymphoma, cervical cancer, ovarian cancer and bladder cancer 47 . In addition, LHX6 was reported to suppress the growth and invasion of breast cancer cells through inhibiting Wnt/β-catenin signaling pathway 31 , and has been putatively identified as a tumor suppressor gene in lung cancer through regulating apoptosis-related genes p53 and Bcl-2, cell cycle-related gene p21 and cell proliferation-associated genes cyclinD1 and c-myc 32 . Since LHX6 was found to promote normal palate development through mediating cell cycle 33 , it is hypothesized that LHX6 may overcome the resistance to EGFR-TKIs in NSCLC through mediating the expression of cell cycle-, apoptosis- and proliferation-associated genes.…”

MiR‐1290 promotes proliferation, migration, and invasion of glioma cells by targeting LHX6

“…LHX6 , a member of the LHX family, participates in the regulation of the central nervous system (Liodis et al, ). Similar with LHX9 , LHX6 was also reported to be silenced in lung cancer (Liu et al, ), and inhibit breast cancer cell propagation and aggressiveness (Hu & Xie, ). Since LHX6 involves in the developmental process of nervous system, it may influence the development of gliomas.…”

“…LHX6, a member of the LHX family, participates in the regulation of the central nervous system (Liodis et al, 2007). Similar with LHX9, LHX6 was also reported to be silenced in lung cancer , and inhibit breast cancer cell propagation and aggressiveness (Hu & Xie, 2015).…”

“…The human LIM homeobox domain (LHX) gene regulates several crucial processes in human cells, including tissue patterning, cell fate specification, and growth (Hobert & Westphal, 2000). Recent studies reported that various LHX genes have been implicated in tumorigenesis (Hu & Xie, 2015). For example, LHX9 gene was silenced in pediatric malignant astrocytomas by hypermethylation and affected glioma cell metastasis (Vladimirova et al, 2009).…”