Breast cancer cell lines have been widely used for breast cancer modelling which encompasses a panel of diseases with distinct phenotypical associations. Though cell lines provide unlimited homogenous materials for tumor studies and are relatively easy to culture, they are known to accumulate mutations duringthe initial establishment and subsequent series of cultivations. Thus, whether breast cancer cell line heterogeneity reflects that of carcinoma remains an important issue to resolve before drawing any reliable conclusion at the tumor level using cell lines. Inconsistent nomenclatures used for breast cancer cell line subtyping and the different number of subtypes grouped for cell lines and tumors make their direct matching elusive. By analyzing the molecular features of 92 breast cancer cell lines as documented by different literatures, we categorize 84 cell lines into 5 groups to be consistent with breast tumor classification. After combing through these cell lines, we summarized the molecular features, genetically and epigenetically, of each subtype, and manually documented 10 cell lines lacking explicit information on subtyping. Nine cell lines, either found inconsistent on their primary molecular features from different studies or being contaminated at the origin, are not suggested as the first choice for experimental use. We conclude that breast tumor cell lines, though having a high mutational frequency with many uncertainties and could not fully capture breast cancer heterogeneity, are feasible but crude models for tumors of the same subtype. New cell lines with enriched interferon regulated genes need to be established to enlarge the coverage of cell lines on tumor heterogeneity.

SUMMARY Familial nonmedullary thyroid cancer accounts for 3 to 9% of all cases of thyroid cancer, but the susceptibility genes are not known. Here, we report a germline variant of HABP2 in seven affected members of a kindred with familial nonmedullary thyroid cancer and in 4.7% of 423 patients with thyroid cancer. This variant was associated with increased HABP2 protein expression in tumor samples from affected family members, as compared with normal adjacent thyroid tissue and samples from sporadic cancers. Functional studies showed that HABP2 has a tumor-suppressive effect, whereas the G534E variant results in loss of function.

The overexpression of NIK plays a critical role in liver inflammatory diseases. Treatment of such diseases with small-molecule NIK inhibitors is a reasonable but underexplored approach. In this paper, we reported the discovery of a potent and selective NIK inhibitor 46 (XT2). 46 inhibited the NIK kinase with an IC50 value of 9.1 nM in vitro, and it also potently suppressed NIK activities in intact cells. In isogenic primary hepatocytes, treatment of 46 efficiently suppressed the expressions of NIK-induced genes. 46 was orally bioavailable in mice with moderate systemic exposure. In a NIK-associated mouse liver inflammation model, 46 suppressed CCl4-induced upregulation of ALT, a key biomarker of acute liver injury. 46 also decreased immune cell infiltration into the injured liver tissue. Overall, these studies provide examples that an NIK inhibitor is able to suppress toxin-induced liver inflammations, which indicates its therapeutic potentials for the treatment of liver inflammatory diseases.

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