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Entity | Breast cancer |
Note | In breast cancers, loss of heterozygosity is often observed on chromosome 6q suggesting a role for LATS1 in breast cancer carcinogenesis (Morinaga et al., 2000). In a study of breast cancer patients, low LATS1 expression has been associated with a biologically aggressive phenotype (Takahashi et al., 2005). In a study of breast cancer tissues, the LATS1 promoter was found to be hypermethylated in 56.7% (17/30) of tumors causing a significant decrease in LATS1 mRNA expression. In breast cancer patients, decreased LATS1 mRNA expression was associated with large tumor size, lymph node metastasis, and estrogen and progesterone negativity. Thus, loss of LATS1 is associated with poor prognosis in breast cancer. |
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Entity | Cervical cancer |
Note | In clinical samples of normal and neoplastic cervix, increased expression of upstream regulator ITCH and decreased expression of LATS1 was associated with transformation of cervical epithelial cells and progression of cervical squamous cell carcinoma (Zhou et al., 2014). In cervical cancer patients high ITCH or low LATS1 expression was associated with increased clinical stage and tumor size. Recently, miRNA-21 (miR-21) was found to regulate LATS1 to promote radioresistance in HR-HPV positive cervical cancer implicating LATS1 in cervical cancer sensitivity to treatment (Liu et al., 2015). |
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Entity | Ovarian cancer |
Note | Lats1 deficient mice develop soft-tissue sarcomas as well as ovarian stromal cell tumours (St John et al., 1999). In human ovarian cancer, reduced LATS1 expression has been observed in ovarian serous borderline cystadenomas and ovarian serous carcinoma while the opposite pattern is found in ovarian mucinous borderline cystadenomas and ovarian mucinous carcinoma (Xu et al., 2015). In clear cell carcinoma, LATS1 expression was decreased. In ovarian serous carcinoma (but not in mucinous or clear cell carcinomas), LATS1 expression levels were correlated with disease recurrence, clinical stage and tumor grade. |
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Entity | Renal cell carcinoma |
Note | LATS1 mRNA expression is reduced in samples from renal cell carcinoma patients (Chen et al., 2014). In these patients, LATS1 expression was associated with cancer pathological grade and clinical stage. The renal cancer cell line 786-O shows hypermethylation of the LATS1 promoter and pharmacological demethylation of the promoter in 786-O reduced cell proliferation while increasing apoptosis and G1 arrest. |
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Entity | Bladder cancer |
Note | A recent study identified 29 total and 18 novel single nucleotide polymorphisms (SNPs) in the LATS1 gene using tissues from urinary bladder or colon cancer patients (Saadeldin et al., 2015). 13 SNPs mapped to intronic and untranslated sequences while 5 SNPs mapped to the coding sequences of LATS1 with 4/5 of these novel SNPs representing missense mutations in the serine/threonine kinase catalytic domain of LATS1. The functional significance of these mutations remains unclear. |
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Entity | Colon cancer |
Note | In tissue from patients with colorectal cancer, the LATS1 gene was found to be hypermethylated in 57% (25/44) of cases and this hypermethylation was associated with decreased LATS1 mRNA levels (Wierzbicki et al., 2013). 89.4% (127/142) of all colorectal cancer samples analyzed showed decreased LATS1 mRNA. Another study identified 18 novel SNPs in the LATS1 gene using tissues from urinary bladder or colon cancer patients (Saadeldin et al., 2015). 13 SNPs mapped to intronic and untranslated sequences while 5 SNPs mapped to the coding sequences of LATS1 with 4/5 of these novel SNPs representing missense mutations in the serine/threonine kinase catalytic domain of LATS1. The functional significance of these SNPs remains poorly understood. |
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Entity | Lung cancer |
Note | In Japanese lung cancer patients, the LATS1 promoter has been found to be hypermethylated in 79.8% (95/119) of tumors (Sasaki et al., 2010). In this study, the methylation status of the LATS1 promoter was associated with squamous histology and smoking status but not patient survival. In a study of non-small cell lung cancer (NSCLC), LATS1 expression is higher in normal lung tissue than in samples from NSCLC tumors (Lin et al., 2014). Low LATS1 expression in NSCLC patients was associated with higher p-TMN stage, increased lymph node metastasis and shorter overall survival. LATS1 overexpression in NSCLC cell lines reduces cell proliferation and invasion. |
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Entity | Nervous system tumors |
Note | LATS1 has been reported to be downregulated in human astrocytomas by promoter hypermethylation (Jiang et al., 2006). In tissues from astrocytomas, 63.66% (56/88) showed hypermethylation of the LATS1 promoter while no methylation of the LATS1 promoter was found in 10 normal brain controls. The LATS1 mRNA level was significantly decreased in hypermethylated astrocytoma tissues compared to unmethylated controls. A similar study has shown that LATS1 is downregulated in gliomas (Ji et al., 2012). In gliomas, decreased LATS1 expression was correlated with higher WHO grade, lower Karnofsky Performance Status and shorter overall survival. Therefore, LATS1 is an independent prognostic indicator for survival of glioma patients. In the glioma cell line U251, overexpression of LATS1 reduced cell proliferation, migration and invasion. Recently, a germline LATS1 mutation (c.286C>T; p.R96W) was identified in a family with Li-Fraumeni syndrome (TP53 germline mutation), a MSH4 germline mutation and multiple cases of nervous system tumours (Kim et al., 2014). Peripheral shwannomas were observed in family members lacking the TP53 mutation but who instead carried mutations in MSH4 and LATS1. To examine how LATS1 might drive sporadic nervous system tumorigenesis, the authors screened 81 sporadic nervous system patients for mutations in the LATS1 gene but only identified one such case (a spinal schwannoma with c.2480delG; p.*R827Kfs*8). |
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Entity | Head and neck squamous cell carcinoma (HNSCC) |
Note | LATS1 is one of 15 tumor-related genes that frequently show promoter hypermethylation in HNSCC (Steinmann et al. 2009). Increased methylation of these tumor-related genes is associated with less cellular differentiation and higher tumor stage. |
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Entity | Oral squamous cell carcinoma |
Note | A pilot study in India examined the methylation status of the LATS1 gene in tumor samples from 13 patients with oral squamous cell carcinoma (Reddy et al., 2015). 54% (7/13) of tumor samples showed hypermethylation of the LATS1 gene. |
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Entity | Soft-tissue sarcoma |
Note | Lats1 deficient mice develop soft-tissue sarcomas as well as ovarian stromal cell tumours (St John et al., 1999). Further, in multiple subtypes of human soft tissue sarcoma (myxoid liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma), a missense point mutation in LATS1 gene locus and reduced LATS1 mRNA levels have been observed (Hisaoka et al., 2002). This decreased expression was suggested to be the result of promoter hypermethylation. |
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Entity | Nevoid basal cell carcinoma syndrome (NBCCS) |
Note | A recent case report describes biallelic disruptions of the LATS1 gene in tissues from a patient with NBCCS (Tate et al., 2014). The authors compared superficial basal cell carcinoma (BCC) cells with more infiltrative BCCs by whole-exome sequencing. The infiltrative but not superficial BCCs showed mutations in the LATS1 gene. Specifically, infiltrative BCCs had one allele with the nonsense mutation c.943C>T (p.Q315X) as well as the loss of the other wild-type allele of LATS1. Loss of heterozygosity analysis showed a deletion in the distal region of chromosome 6q. |
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