HIF‐1α interacts with Kindlin‐2 and influences breast cancer elasticity: A study based on shear wave elastography imaging

Breast cancer was the most frequent and the second most deadly cancer in women in 2018 in China; thus, early diagnosis of breast cancer is important. Studies have reported that tissue stiffness promotes cancer progression through increased collagen or fibrosis. Shear wave elastography (SWE) is a technique for measuring tissue stiffness. However, the mechanisms underlying cancer tissue stiffness or fibrosis are not entirely clear. Hypoxia‐inducible factor 1 (HIF‐1α) is expressed in response to hypoxia and contributes to tumor progression and metastasis. Kindlin‐2 is an important co‐activator of integrin. We have reported that Kindlin‐2 influences breast cancer stiffness and metastasis. In this study, SWE was used to determine the maximum elasticity (E(max)) of patients before operation or core needle biopsy. The specimens were used for staining. Knockdown, overexpression, co‐immunoprecipitation, and immunofluorescence assays were used to explore the relationship between HIF‐1α and Kindlin‐2. We found that HIF‐1α and Kindlin‐2 were highly expressed in invasive breast cancer and that the expression levels of HIF‐1α and Kindlin‐2 were correlated with E(max). HIF‐1α interacts with Kindlin‐2. Besides, HIF‐1α and Kindlin‐2 influence the expression of P4HA1, an important protein in collagen biogenesis through the integrin/FAK pathway. Our study first identified a new mechanism of invasive breast cancer stiffness by linking HIF‐1α and Kindlin‐2 to collagen biogenesis. Therefore, based on SWE, E(max) could be a physical biomarker of invasive breast cancer for early, noninvasive diagnosis, and HIF‐1α and Kindlin‐2 could be pathological markers for early diagnosis and targeted therapy.