Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key factor in the regulation of breast cancer differentiation and metastasis, its potential role in modulating tumor chemoresistance has not been fully understood. Here, through the study of specimens from a large cohort of human breast cancer subjects, we showed that patients with tumors that expressed high levels of ZEB1 responded poorly to chemotherapy. Moreover, ZEB1 expression was positively correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1, which are key components of tumor chemoresistant mechanisms. At the molecular level, ectopic expression of ZEB1 impaired the responsiveness of breast cancer cells to genotoxic drug treatment, such as epirubicin (EPI). During this process, ZEB1 transcriptionally activated the expression of ataxia-telangiectasia mutated (ATM) kinase by forming a ZEB1/p300/PCAF complex on its promoter, leading to increased homologous recombination (HR)-mediated DNA damage repair and the clearance of DNA breaks. Using a nude mouse xenograft model, we further confirmed that ectopic expression of ZEB1 decreased breast cancer responsiveness to EPI treatment in vivo. Collectively, our findings suggest that ZEB1 is a crucial determinant of chemotherapeutic resistance in breast cancer.

Antiestrogen resistance is a major obstacle to endocrine therapy for breast cancers. Although reduced estrogen receptor-α (ER-α) expression is a known contributing factor to antiestrogen resistance, the mechanisms of ER-α downregulation in antiestrogen resistance are not fully understood. Here, we report that ectopic zinc-finger E-box binding homeobox 1 (ZEB1) is associated with ER-α deficiency in breast cancer cells and thus confers antiestrogen resistance. Mechanistically, ZEB1 represses ER-α transcription by forming a ZEB1/DNA methyltransferase (DNMT)3B/histone deacetylase (HDAC)1 complex on the ER-α promoter, leading to DNA hypermethylation and the silencing of ER-α. Thus, ectopic ZEB1 downregulates ER-α expression and subsequently attenuates cell growth inhibition by antiestrogens, such as tamoxifen and fulvestrant. Notably, the depletion of ZEB1 by RNA interference causes ER-α promoter demethylation, restores ER-α expression, and increases the responsiveness of breast cancer cells to antiestrogen treatment. By studying specimens from a large cohort of subjects with breast cancer, we found a strong inverse correlation between ZEB1 and ER-α protein expression. Moreover, breast tumors that highly express ZEB1 exhibit ER-α promoter hypermethylation. Using a nude mouse xenograft model, we further confirmed that the downregulation of ZEB1 expression restores the responsiveness of breast cancer cells to antiestrogen therapy in vivo. Therefore, our findings suggest that ZEB1 is a crucial determinant of resistance to antiestrogen therapies in breast cancer.

Laminaria longissima and ZaohouchengNo.1 (a commercial variety selected from Laminaria japonica) differ to a certain extent in their morphological characteristics and biological habits. It was assumed that varieties bred through their hybridization should exhibit high yield potential and tolerate relatively high seawater temperatures. Female gametophyte clones isolated from L. longissima were crossed with male clones isolated from Zaohoucheng No.1. Laminaria variety 90-1 was obtained after gametophyte crossing, continuous self-crossing and selection. This variety was genetically homozygous; the indices of variation of blade length, width and thickness of the final two selection cycles were 7-8%; i.e., not different significantly. Variety 90-1 grew faster, lost less tissue and had higher yield potential than two widely used commercial varieties of L. japonica (all commercial varieties currently used in China originate from this latter species). The blade of variety 90-1 increased 3.71 cm day −1 on average during the whole period of cultivation, almost twofold that of two controls, and growth was maintained even when seawater temperature was higher than 18°C -3°C higher than the temperature tolerated by other Laminaria varieties. Variety 90-1 increased yield by more than 70% over two controls and also synthesized desirable amounts of iodine, mannitol and algin. In blade length, variety 90-1 was more similar to L. longissima than to L. japonica, but more similar to L. japonica in blade width and thickness. Since the adoption of variety 90-1 in 1999, its culturing area has increased each year to reach its current area of 7,000 ha, i.e., almost one-third of the total cultivation acreage of Laminaria in China. Breeding of variety 90-1 has demonstrated that it is feasible to develop elite Laminaria varieties by crossing gametophytes from different Laminaria species in combination with successive self-crossing and selection.

Globally, China has the largest scale of kelp cultivation and production operations. However, its kelp aquaculture industry is suffering from declining germplasm diversity, degradation of agronomic traits, the presence of polluted environments, changing ocean conditions and increasing anthropological interference. This review covers two of the most commercially important kelp species in China, viz. Saccharina japonica and Undaria pinnatifida. It summarizes the history of their cultivation, production, economic and ecological benefits, their breeding programmes (e.g. inter-and intra-specific hybridization and marker-assisted selection) and efforts towards population genetic diversity and conservation. The article focuses on three significant challenges, for example genetic crosscontamination between the wild and farmed kelp populations, ocean warming and ocean acidification. Accordingly, we outline the steps required to provide several intervention measures, for example (i) collection and preservation of wild and cultivated kelp germplasm; (ii) selection of suitable cultivation sites under changing environmental conditions; (iii) developing stress-resistant cultivars; and finally, (iv) adoption of innovative cultivation models. The review concludes with genome-based, designs for molecular breeding and calls for the establishment of an East Asian Kelp Consortium (EAKC). Collectively, the Chinese kelp industry could provide beneficial goods and services, for example bioenergy to fine chemicals and environmental benefits, such as carbon capture, pH amelioration and provision of habitat for many other marine species of commercial value. The strategies proposed in this article thus have the potential to not only improve but also reinvigorate the kelp industry in China and nearby Japan and Korea, in the context of both environmental health and economic benefits.