SummaryAdipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with interleukin-6 are deficient in the Hedgehog pathway, and their differentiation capability is associated with increased ciliary disassembly genes like AURKA. Interestingly, inhibition of Aurora A or its downstream target the histone deacetylase 6 rescues the cilium length and function of obese ASCs. This work highlights a mechanism whereby defective cilia render ASCs dysfunctional, resulting in diseased adipose tissue. Impaired cilia in ASCs may be a key event in the pathogenesis of obesity, and its correction might provide an alternative strategy for combating obesity and its associated diseases.

Adipose-derived mesenchymal stem cells (ASCs) are considered to be a useful tool for regenerative medicine, owing to their capabilities in differentiation, self-renewal, and immunomodulation. These cells have become a focus in the clinical setting due to their abundance and easy isolation. However, ASCs from different depots are not well characterized. Here, we analyzed the functional similarities and differences of subcutaneous and visceral ASCs. Subcutaneous ASCs have an extraordinarily directed mode of motility and a highly dynamic focal adhesion turnover, even though they share similar surface markers, whereas visceral ASCs move in an undirected random pattern with more stable focal adhesions. Visceral ASCs have a higher potential to differentiate into adipogenic and osteogenic cells when compared to subcutaneous ASCs. In line with these observations, visceral ASCs demonstrate a more active sonic hedgehog pathway that is linked to a high expression of cilia/differentiation related genes. Moreover, visceral ASCs secrete higher levels of inflammatory cytokines interleukin-6, interleukin-8, and tumor necrosis factor α relative to subcutaneous ASCs. These findings highlight, that both ASC subpopulations share multiple cellular features, but significantly differ in their functions. The functional diversity of ASCs depends on their origin, cellular context and surrounding microenvironment within adipose tissues. The data provide important insight into the biology of ASCs, which might be useful in choosing the adequate ASC subpopulation for regenerative therapies.

RITA, the RBP‐J interacting and tubulin‐associated protein, has been reported to be related to tumor development, but the underlying mechanisms are not understood. Since RITA interacts with tubulin and coats microtubules of the cytoskeleton, we hypothesized that it is involved in cell motility. We show here that depletion of RITA reduces cell migration and invasion of diverse cancer cell lines and mouse embryonic fibroblasts. Cells depleted of RITA display stable focal adhesions (FA) with elevated active integrin, phosphorylated focal adhesion kinase, and paxillin. This is accompanied by enlarged size and disturbed turnover of FA. These cells also demonstrate increased polymerized tubulin. Interestingly, RITA is precipitated with the lipoma‐preferred partner (LPP), which is critical in actin cytoskeleton remodeling and cell migration. Suppression of RITA results in reduced LPP and α‐actinin at FA leading to compromised focal adhesion turnover and actin dynamics. This study identifies RITA as a novel crucial player in cell migration and invasion by affecting the turnover of FA through its interference with the dynamics of actin filaments and microtubules. Its deregulation may contribute to malignant progression.

Breast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Adipose tissue is the major microenvironment of breast cancer. Obesity changes the composition, structure, and function of adipose tissue, which is associated with inflammation and metabolic dysfunction. Interestingly, adipose tissue is rich in ASCs/MSCs, and obesity alters the properties and functions of these cells. As a key component of the mammary stroma, ASCs play essential roles in the breast cancer microenvironment. The crosstalk between ASCs and breast cancer cells is multilateral and can occur both directly through cell–cell contact and indirectly via the secretome released by ASC/MSC, which is considered to be the main effector of their supportive, angiogenic, and immunomodulatory functions. In this narrative review, we aim to address the impact of obesity on ASCs/MSCs, summarize the current knowledge regarding the potential pathological roles of ASCs/MSCs in the development of breast cancer, discuss related molecular mechanisms, underline the possible clinical significance, and highlight related research perspectives. In particular, we underscore the roles of ASCs/MSCs in breast cancer cell progression, including proliferation and survival, angiogenesis, migration and invasion, the epithelial–mesenchymal transition, cancer stem cell development, immune evasion, therapy resistance, and the potential impact of breast cancer cells on ASCS/MSCs by educating them to become cancer-associated fibroblasts. We conclude that ASCs/MSCs, especially obese ASCs/MSCs, may be key players in the breast cancer microenvironment. Targeting these cells may provide a new path of effective breast cancer treatment.