Cancer is recognized globally as one of the most costly and deadly health problems, with lung cancer being the leading cause of cancer related deaths. Lung cancer is classified into two major categories, nonsmall cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with NSCLC accounting for about 85% of all lung cancers. When NSCLC is detected early, patients have a 70% chance of being alive 5 years later. When NSCLC is detected at an advanced stage, the 5-year survival prediction drops to less than 10%.
The poor survival rate is mainly attributable to regional or distant metastasis. Although metastasis is the principal event leading to lung cancer deaths, its molecular basis remains poorly understood. Now, a study from researchers at the National Cheng-Kung University has identified a biomarker which detects the most common lung cancer, NSCLC, in its earliest stages; a discovery that could one day change how long lung cancer patients live. The team state that to their knowledge theirs is the first study to describe HIP1 involvement in the progression of NSCLC. The opensource study is published in American Journal of Respiratory and Critical Medicine.
Previous studies show that the huntingtin interacting protein1 (HIP1) is a 116kDa protein which plays a role in tumourigenesis by providing evidence of overexpression in various human malignancies and transforming fibroblasts. Although HIP1 associates with human cancer biology, its precise role in tumour progression remains unknown. Therefore, the lab wanted to test HIP1 as a potential new biomarker and investigate its role in lung cancer progression and metastasis, the cause of most lung cancer deaths. The current study shows that in addition to serving as a biomarker, HIP1 represses the mobility of lung cancer cells in laboratory studies and suppresses metastasis in a mouse model of the cancer.
The current study examined lung tissue from 121 patients. Results show that those in the earliest stages of the diseases expressed more HIP1 than those in the later stages of the disease. Data findings show a significant correlation between those patients in early stages of the disease (stage I-II) who expressed higher levels of HIP1 and longer survival, indicating that HIP1 was a prognostic biomarker.
The group then investigated the correlation between HIP1 and cellular mobility in vitro and in a mouse model of adenocarcinoma with results showing that HIP1 expression was inversely associated with cancer cell mobility. The lab confirmed those results in their mouse model with high levels of HIP1 expression significantly associated with fewer metastatic tumour cells. When observing the mechanisms behind HIP1’s ability to suppress cellular mobility and metastasis, data findings show that HIP1 modulates Akt, a protein kinase that regulates the epithelial-mesenchymal transition, which in turn facilitates cell invasion and the beginning of metastasis.
The team surmise that if HIP1 levels and functions can be restored, human lung cancer metastasis in the early stage can be prevented or stopped. For the future, the researchers state that to bring this discovery to clinical care, they now need to identify the regulatory factors of the HIP1 gene that are targetable through gene therapy or small molecule interventions.
Source: National Cheng-Kung University