The role of DYNLT3 in breast cancer proliferation, migration, and invasion via epithelial‐to‐mesenchymal transition

Abstract

PurposeDYNLT3 is identified as an age‐related gene. Nevertheless, the specific mechanism of its carcinogenesis in breast tumor has not been clarified. This research aims to elucidate the role and the underlying molecular pathways of DYNLT3 on breast cancer tumorigenesis.MethodsThe differential expression of DYNLT3 among breast cancer, breast fibroids, and normal tissues, as well as in various breast cancer cell lines were detected by immunohistochemical staining, real‐time quantitative reverse transcription‐PCR and Western blotting, respectively. Additionally, the role of DYNLT3 on cell viability and proliferation were observed through cell counting kit‐8, bromodeoxyuridine, and colony formation experiments. Migratory and invasive abilities was envaulted by wound healing and Transwell methods. Apoptotic cells rate was examined by flow cytometry. Furthermore, nude mice xenograft models were established to confirm the role of DYNLT3 in tumor formation in vivo.ResultsDYNLT3 expression was highly rising in both breast cancer tissues and cells. DYNLT3 knockdown obviously suppressed cell growth, migration and invasion, and induced cell apoptosis in MDA‐MB‐231 and MCF‐7 breast cancer cells. The overexpression of DYNLT3 exerted the opposite effect in MDA‐MB‐231 cells. Moreover, DYNLT3 knockdown inhibited tumor formation in vivo. Mechanistically, an elevation of N‐cadherin and vimentin levels and a decline of E‐cadherin were observed when DYNLT3 was upregulated, which was reversed when DYNLT3 knockdown was performed.ConclusionDYNLT3 may function as a tumor‐promotor of age‐associated breast cancer, which is expected to provide experimental basis for new treatment options.

Biological Basis of Breast Cancer-Related Disparities in Precision Oncology Era

“…It is known that specific breast cancer 1/2 (BRCA1/2) mutations in the worldwide population are highly ethnic-specific [30], with a high frequency of BRCA variation in specific countries or ethnic groups, especially within genetically isolated populations, where these mutations are descendent from a single founder [41]. Wang (2023) summarized the main factors that contribute to the ethnic specificity of the BRCA variation, such as strong positive selection on human BRCA, adaptation to the living environment, genetic drift and founder variation in different ethnic populations [30]. BRCA1 and BRCA2 mutations are estimated to be responsible for about 3% of all BCs and other less common high-penetrance genes account for less than 1% of all BCs [42].…”

“…Among these deregulated genes, dynein light chain Tctex-type 3 (DYNLT3), prolyl 4-hydroxylase subunit alpha 3 (P4HA3) and Aristaless-like homeobox 4 (ALX4) have been identified as age-related genes that play a significant role in BC progression [141]. Thus, DYNLT3 was found to be highly overexpressed in both BC tissues and BC cell lines, in association with N-cadherin and vimentin (VIM) overexpression associated with E-cadherin downregulation, while DYNLT3 silencing suppressed cell growth, migration and invasion via the epithelial-mesenchymal transition (EMT) and induced cell apoptosis in MDA-MB-231 and MCF7 BC cells [142]. Interestingly, Aktary et al (2021) showed that the level of DYNLT3 is dependent on β-catenin activity, revealing a function of the canonical Wnt/β-catenin signaling pathway during melanocyte and skin pigmentation [143].…”